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Virchows Archiv

, Volume 425, Issue 1, pp 3–24 | Cite as

Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity

  • Annette Schmitt-Gräff
  • Alexis Desmoulière
  • G. Gabbiani
  • A. Schmitt-Gräff
  • A. Desmoulière
Review Article

Abstract

Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of α-SM actin, the actin isoform present in SM cells and myoepithelial cells and particularly abundant in vascular SM cells. Myofibroblasts have been suggested to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. When contraction stops and the wound is fully epithelialized, myofibroblasts containing α-SM actin disappear, probably as a result of apoptosis, and the scar classically becomes less cellular and composed of typical fibroblasts with well-developed rough endoplasmic reticulum but with no more microfilaments. In contrast, α-SM actin expressing myofibroblasts persist in hypertrophic scars and in fibrotic lesions of many organs, including stroma reaction to epithelial tumours, where they are allegedly involved in retractile phenomena as well as in extracellular matrix accumulation. The mechanisms leading to the development of myofibroblastic features remain to be investigated. In vivo and in vitro investigations have shown that γ-interferon exerts an antifibrotic activity at least in part by decreasing α-SM actin expression whereas heparin increases the proportion of α-SM actin positive cells. Recently, we have observed that the subcutaneous administration of transforming growth factor-β1 to rats results in the formation of a granulation tissue in which α-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor, basic fibroblast growth factor and tumour necrosis factor-α, despite their profibrotic activity, do not induce α-SM actin in myofibroblasts. In conclusion, fibroblastic cells are relatively undifferentiated and can assume a particular phenotype according to the physiological needs and/or the microenvironmental stimuli. Further studies on fibroblast adaptation phenomena appear to be useful for the understanding of the mechanisms of development and regression of pathological processes such as wound healing and fibrocontractive diseases.

Key words

Cytoskeleton Wound healing Fibrosis Extracellular matrix Cytokine 

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References

  1. 1.
    Abercrombie M, Flint MH, James DW (1956) Wound contraction in relation to collagen formation in scorbutic guinea pigs. J Embryol Exp Morphol 4:167–175Google Scholar
  2. 2.
    Albers K, Fuchs E (1992) The molecular biology of intermediate filament proteins. Int Rev Cytol 134:243–279Google Scholar
  3. 3.
    Alpers CE, Hudkins KL, Gown AM, Johnson RJ (1992) Enhanced expression of “muscle-specific” actin in glomerulonephritis. Kidney Int 41:1134–1142PubMedGoogle Scholar
  4. 4.
    Amento EP, Deguzman L, Lee WP, Xu Y, McFatridge L, Beck LS (1991) The systemic administration of TGF-β1 accelerates wound healing. J Cell Biochem [Suppl] 15F:191Google Scholar
  5. 5.
    Antoniades HN, Galanopoulos T, Neville-Golden J, Kiritsy CP, Lynch SE (1991) Injury induces in vivo expression of platelet-derived growth factor (PDGF) and PDGF receptor mRNAs in skin epidermal cells and PDGF mRNA in connective tissue fibroblasts. Proc Natl Acad Sci USA 88:565–569Google Scholar
  6. 6.
    Appleton I, Tomlinson A, Chander CL, Willoughby DA (1992) Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. Lab Invest 67:703–710Google Scholar
  7. 7.
    Babij P, Zhao J, White S, Woodcock-Mitchell J, Mitchell J, Absher M, Baldor L, Periasamy M, Low RB (1993) Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells. Am J Physiol 265:L127-L132Google Scholar
  8. 8.
    Badalamente MA, Hurst LC, Grandia SK, Sampson SP (1992) Platelet-derived growth factor in Dupuytren's disease. J Hand Surg Am 17:317–323Google Scholar
  9. 9.
    Baird A, Mormede P, Bohlen P (1985) Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochem Biophys Res Commun 126:358–364Google Scholar
  10. 10.
    Ballardini G, Fallani M, Biagini G, Bianchi FB, Pisi E (1988) Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis. Virchows Arch [B] 56:45–49Google Scholar
  11. 11.
    Bandman E (1985) Myosin isoenzyme transitions in muscle development, maturation, and disease. Int Rev Cytol 37:97–131Google Scholar
  12. 12.
    Barrett TB, Benditt EP (1987) Sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. Proc Natl Acad Sci USA 84:1099–1103Google Scholar
  13. 13.
    Basset P, Bellocq JP, Wolf C, Stoll J, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P (1990) A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348:699–704Google Scholar
  14. 14.
    Bauer EA, Cooper TW, Huang JS, Altman J, Deuel TS (1985) Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor. Proc Natl Acad Sci USA 82:4132–4136Google Scholar
  15. 15.
    Bayreuther K, Rodemann HP, Hommel R, Dittmann K, Albiez M, Francz PI (1988) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci USA 85:5112–5116Google Scholar
  16. 16.
    Bayreuther K, Francz PI, Gogol J, Hapke C, Maier M, Meinrath HG (1991) Differentiation of primary and secondary fibroblasts in cell culture systems. Mutat Res 256:233–242Google Scholar
  17. 17.
    Bayreuther K, Francz PI, Rodemann HP (1992) Fibroblasts in normal and pathological terminal differentiation, ageing, apoptosis and transformation. Arch Gerontol Geriatr 3:47–74Google Scholar
  18. 18.
    Becker CG (1972) Demonstration of actomyosin in mesangial cells of the renal glomerulus. Am J Pathol 66:97–110Google Scholar
  19. 19.
    Beertsen W, Events V, Van den Hoof A (1974) Fine structure of fibroblasts in the periodontal ligament of the rat incisor and their possible role in tooth eruption. Arch Oral Biol 19:1097–1098Google Scholar
  20. 20.
    Bell E, Marek LF, Levinstone DS, Merrill C, Sher S, Young IT, Eden M (1978) Loss of division potential in vitro: aging or differentiation? Departure of cells from cycle may not be a sign of aging, but a sign of differentiation. Science 202:1158–1163Google Scholar
  21. 21.
    Bellows CG, Melcher AH, Aubin JE (1981) Contraction and organization of collagen gels by cell cultured from periodontal ligament, gingiva and bone suggest functional differences between cell types. J Cell Sci 211:1052–1054Google Scholar
  22. 22.
    Benjamin SP, Mercer RD, Hawk WA (1977) Myofibroblast contraction in spontaneous regression of multiple congenital mesenchymal hamartomas. Cancer 40:2343–2352Google Scholar
  23. 23.
    Benzonana G, Skalli O, Gabbiani G (1988) Correlation between the distribution of smooth muscle or nonmuscle myosins and α-smooth muscle actin in normal and pathological soft tissues. Cell Motil Cytoskeleton 11:260–273Google Scholar
  24. 24.
    Bershadsky AD, Vasiliev JM (1988) Cytoskeleton. Plenum Press, New YorkGoogle Scholar
  25. 25.
    Björkerud S (1991) Effects of transforming growth factor-β1 on human arterial smooth muscle cells in vitro. Arterioscler Thromb 11:892–902Google Scholar
  26. 26.
    Blatti SP, Foster DN, Ranganathan G, Moses HL, Getz MJ (1988) Induction of fibronectin gene transcription and mRNA is a primary response to growth factor stimulation of AKR-2B cells. Proc Natl Acad Sci USA 85:1119–1123Google Scholar
  27. 27.
    Blau HM, Baltimore D (1991) Differentiation requires continuous regulation. J Cell Biol 112:781–783Google Scholar
  28. 28.
    Blobel GA, Moll R, Franke WW, Kayser KW, Gould VE (1984) The intermediate filament cytoskeleton of malignant mesotheliomas and its diagnostic significance. Am J Pathol 121:235–247Google Scholar
  29. 29.
    Bochaton-Piallat ML, Gabbiani F, Ropraz P, Gabbiani G (1992) Cultured aortic smooth muscle cells from newborn and adult rats show distinct cytoskeletal features. Differentiation 49:175–185Google Scholar
  30. 30.
    Bolen JW, Hammar SP, McNutt MA (1986) Reactive and neoplastic serosal tissue: a light microscopic, ultrastructural, and immunocytochemical study. Am J Surg Pathol 10:34–47Google Scholar
  31. 31.
    Bolmont C, Anduyard M, Peyrol S, Grimaud JA (1991) Desmin expression in fibroblasts of murine periovular granuloma during liver Schistosoma mansoni infection. Differentiation 46:89–95Google Scholar
  32. 32.
    Border WA, Ruoslahti E (1992) Transforming growth factor-β in disease: the dark side of tissue repair. J Clin Invest 90:1–7Google Scholar
  33. 33.
    Border WA, Noble NA, Yamamoto T, Harper JR, Yamaguchi Y, Pierschbacher MD, Ruoslahti E (1992) Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease. Nature 360:361–364Google Scholar
  34. 34.
    Borrione AC, Zanellato AM, Giuriato L, Scannapieco G, Pauletto P, Sartore S (1990) Non-muscle and smooth muscle myosin isoforms in bovine endothelial cells. Exp Cell Res 190:1–10Google Scholar
  35. 35.
    Bossy-Wetzel E, Bravo R, Hanahan D (1992) Transcription factors jun B and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development. Gen Dev 6:2340–2351Google Scholar
  36. 36.
    Boswell CA, Majno G, Joris I, Ostrom KA (1992) Acute endothelial cell contraction in vitro: A comparison with vascular smooth muscle cells and fibroblasts. Microsvasc Res 43:178–191Google Scholar
  37. 37.
    Boya J, Carbonell AL, Martinez A (1988) Myofibroblasts in human palatal mucosa. Acta Anat 131:161–165Google Scholar
  38. 38.
    Bressler RS (1973) Myoid cells in the capsule of the adrenal gland and in monalayers derived from cultured adrenal capsules. Anat Rec 177:525–531Google Scholar
  39. 39.
    Brinckerhoff CE, Guyre PM (1985) Increased proliferation of human synovial fibroblasts treated with recombinant immune interferon. J Immunol 134:3142–3146Google Scholar
  40. 40.
    Brinckerhoff CE, Nagel JE (1981) Collagenase production by cloned populations of rabbit synovial fibroblasts. Coll Res 1:433–444Google Scholar
  41. 41.
    Brown KD, Littlewood CJ (1989) Endothelin stimulates DNA synthesis in Swiss 3T3 cells. Synergy with polypeptide growth factors. Biochem J 263:977–980Google Scholar
  42. 42.
    Brown MR, Vaughan J, Jimenez LL, Vale W, Baird A (1991) Transforming growth factor-β: role in mediating serum-induced endothelin production by vascular endothelial cells. Endocrinology 129:2355–2360Google Scholar
  43. 43.
    Bruce SA (1991) Ultrastructure of dermal fibroblasts during development and aging: Relationship to in vitro senescence of dermal fibroblasts. Exp Geront 26:3–16Google Scholar
  44. 44.
    Buoro S, Ferrarese P, Chiavegato A, Roelofs M, Scatena M, Pauletto P, Passerini-Glazel G, Pagano F, Sartore S (1993) Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab Invest 69:589–602Google Scholar
  45. 45.
    Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJS, Aglietta M, Arese P, Mantovani A (1989) Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337:471–473Google Scholar
  46. 46.
    Caplan AI, Fiszman MY, Eppenberger HM (1983) Molecular and cell isoforms during development. Science 221:921–927Google Scholar
  47. 47.
    Carrel A (1922) Growth-promoting function of leucocytes. J Exp Med 36:385–391Google Scholar
  48. 48.
    Carrel A, Hartmann A (1916) Cicatrization of wounds. I. The relation between the size of a wound and the rate of its cicatrization. J Exp Med 24:429–450Google Scholar
  49. 49.
    Chamley-Campbell JH, Campbell GR (1981) What controls smooth muscle phenotype? Atherosclerosis 40:347–357Google Scholar
  50. 50.
    Chamley-Campbell J, Campbell GR, Ross R (1979) The smooth muscle cell in culture. Physiol Rev 59:2–39Google Scholar
  51. 51.
    Charbord P, Gown AM, Keating A, Singer JW (1985) CGA-7 and HHF, two monoclonal antibodies that recognize muscle actin and react with adherent cells in human long term bone marrow cultures. Blood 66:1138–1142Google Scholar
  52. 52.
    Charbord P, Lerat H, Newton I, Tamayo E, Gown AM, Singer JW, Herve P (1990) The cytoskeleton of stromal cells from human bone marrow cultures resembles that of cultured smooth muscle cells. Exp Hematol 18:276–282Google Scholar
  53. 53.
    Cheney RE, Riley MA, Mooseker MS (1993) Phylogenetic analysis of the myosin superfamily. Cell Motil Cytoskeleton 24:215–223Google Scholar
  54. 54.
    Chiavegato A, Scatena M, Roelofs M, Ferrarese P, Pauletto P, Passerini-Glazel G, Pagano F, Sartore S (1993) Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder. Exp Cell Res 207:310–320Google Scholar
  55. 55.
    Cintorino M, Bellizi de Marco E, Leoncini P, Tripodi SA, Ramaekers FC, Sappino AP, Schmitt-Gräff A, Gabbiani G (1991) Expression of α-smooth muscle actin in stromal cells of the uterine cervix during epithelial neoplastic changes. Int J Cancer 47:843–846Google Scholar
  56. 56.
    Claman HN (1985) Mast cells, T cells and abnormal fibrosis. Immunol Today 6:192–195Google Scholar
  57. 57.
    Clark SC, Kamen R (1987) The human hematopoietic colony-stimulating factors. Science 236:1229–1237Google Scholar
  58. 58.
    Clowes AW, Karnovsky MJ (1977) Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature 265:625–626Google Scholar
  59. 59.
    Clowes AW, Clowes MM, Kocher O, Ropraz P, Chaponnier C, Gabbiani G (1988) Arterial smooth muscle cells in vivo: relationship between actin isoform expression and mitogenesis and their modulation by heparin. J Cell Biol 107:1939–1945Google Scholar
  60. 60.
    Colombi RP (1993) Sarcomatoid carcinomas of the female genital tract (malignant mixed Mullerian tumors). Semin Diagn Pathol 10:169–175Google Scholar
  61. 61.
    Corjay MH, Blank RS, Owens GK (1990) Platelet-derived growth factor-induced destabilization of smooth muscle alpha-actin mRNA. J Cell Physiol 145:391–397Google Scholar
  62. 62.
    Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, Norton JA (1987) Transforming growth factor β levels in rat wound chambers. J Surg Res 42:622–628Google Scholar
  63. 63.
    Czaja MJ, Weiner FR, Flanders KC, Giambrone MA, Wind R, Bimpica L, Zern MA (1989) In vitro and in vivo association of transforming growth factor-β 1 with hepatic fibrosis. J Cell Biol 108:2477–2482Google Scholar
  64. 64.
    Czernobilsky B, Shezen E, Lifschitz-Mercer B, Fogel M, Luzon A, Jacob N, Skalli O, Gabbiani G (1989) Alpha smooth muscle actin (α-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasma. Virchows Arch [B] 57:55–61Google Scholar
  65. 65.
    Darby I, Skalli O, Gabbiani G (1990) α-Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest 63:21–29Google Scholar
  66. 66.
    Davidson JM, Klagsbrun M, Hill KE, Buckley A, Sullivan R, Brewer PS, Woodward SC (1985) Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor. J Cell Biol 100:1219–1227Google Scholar
  67. 67.
    Dedhar S, Gaboury L, Galloway P, Eaves C (1988) Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. Proc Natl Acad Sci USA 85:9253–9257Google Scholar
  68. 68.
    Desmoulière A, Rubbia-Brandt L, Gabbiani G (1991) Modulation of actin isoform expression in cultured arterial smooth muscle cells by heparin and culture conditions. Arterioscler Thromb 11:244–253Google Scholar
  69. 69.
    Desmoulière A, Rubbia-Brandt L, Abdiu A, Walz T, Macieira-Coelho A, Gabbiani G (1992) α-Smooth muscle actin is expressed in a subpopulation of cultured and cloned fibroblasts and is modulated by γ-interferon. Exp Cell Res 201:64–73Google Scholar
  70. 70.
    Desmoulière A, Rubbia-Brandt L, Grau G, Gabbiani G (1992) Heparin induces α-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts. Lab Invest 67:716–726Google Scholar
  71. 71.
    Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111Google Scholar
  72. 72.
    Donjacour AD, Cunha GR (1991) Stromal regulation of epithelial function. In: Lipmann M, Dickson R (eds) Regulatory mechanisms in breast cancer. Kluwer Academic Publishers, Boston, pp 335–364Google Scholar
  73. 73.
    Duncan MR, Berman B (1985) γ Interferon is the lymphokine and β interferon the monokine responsible for inhibition of fibroblast collagen production and late but not early fibroblast proliferation. J Exp Med 162:516–527Google Scholar
  74. 74.
    Dvorak HF (1986) Tumors: wounds that do not heal. N Engl J Med 315:1650–1659Google Scholar
  75. 75.
    Dvorak AM, Furitsu T, Estrella P, Ishizaka T (1991) Human lung-derived mature mast cells cultured alone or with mouse 3T3 fibroblasts maintain an ultrastructural phenotype different from that of human mast cells that develop from human cord blood cells cultured with 3T3 fibroblasts. Am J Pathol 139:1309–1318Google Scholar
  76. 76.
    Eddy RJ, Petro JA, Tomasek JJ (1988) Evidence for the non-muscle nature of the “myofibroblast” of granulation tissue and hypertrophic scar. An immunofluorescence study. Am J Pathol 130:252–260Google Scholar
  77. 77.
    Edel G, Roessner A, Deneke B, Wormann B (1992) Morphological heterogeneity and phenotypic instability versus metastatic stability in the musine tumor model ER 15-P. J Cancer Res Clin Oncol 118:349–360Google Scholar
  78. 78.
    Elias JA, Jimenez SA, Freundlich B (1987) Recombinant gamma, alpha, and beta interferon regulation of human lung fibroblast proliferation. Am Rev Respir Dis 135:62–65Google Scholar
  79. 79.
    Enzinger FM, Weiss SW (1988) Soft tissue tumours. Mosby, St. LouisGoogle Scholar
  80. 80.
    Eyden BP, Banerjie SS, Harris M (1991) A study of spindle cell sarcoma showing myofibroblastic differentiation. Ultrastruct Pathol 15:367–378Google Scholar
  81. 81.
    Fabra A, Nakajima M, Bucana CD, Fidler IJ (1992) Modulation of the invasive phenotype of human colon carcinoma cells by organ specific fibroblasts of nude mice. Differentiation 52:101–110Google Scholar
  82. 82.
    Feiner H, Kaye GJ (1976) Ultrastructural evidence of myofibroblasts in circumscribed fibromatosis. Arch Pathol Lab Med 100:265–268Google Scholar
  83. 83.
    Fina M, Bresnick S, Baird A, Ryan A (1991) Improved healing of tympanic membrane perforations with basic fibroblast growth factor. Growth Factors 5:265–272Google Scholar
  84. 84.
    Flaumenhaft R, Rifkin DB (1991) Extracellular matrix regulation of growth factor and protease activity. Curr Opin Cell Biol 3:817–823Google Scholar
  85. 85.
    Flaumenhaft R, Kojima S, Abe M, Rifkin DB (1993) Activation of latent transforming growth factor β. Adv Pharmacol 24:51–76Google Scholar
  86. 86.
    Fletcher CMD, Stirling RW (1990) Intranodal myofibroblastoma presenting in the submandibular region; evidence of a broader clinical and histopathological spectrum. Histopathology 16:287–294Google Scholar
  87. 87.
    Floege J, Johnson RJ, Gordon K, Jida H, Pritzl P, Yoshimura A, Campbell C, Alpers CE, Couser WG (1991) Increased synthesis of extracellular matrix in mesangial proliferative nephritis. Kidney Int 40:477–488Google Scholar
  88. 88.
    Franke WW, Schinko W (1969) Nuclear shape in muscle cells. J Cell Biol 42:326–331Google Scholar
  89. 89.
    Franke WW, Schmid E, Osborn M, Weber K (1978) Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci USA 75:5034–5038Google Scholar
  90. 90.
    Fredj-Reygrobellet D, Plouet J, Delayre T, Baudouin C, Bourret F, Lapalus P (1986) Effects of aFGF and bFGF on wound healing in rabbit corneas. Curr Eye Res 6:1205–1209Google Scholar
  91. 91.
    Friedman SL (1993) The cellular basis of hepatic fibrosis — mechanisms and treatment strategies. N Engl J Med 328:1829–1835Google Scholar
  92. 92.
    Fujita H, Tatsumi H, Ban T, Tamura S (1986) Fine-structural characteristics of the liver of the cod (Gadus morhua macrocephalus). Cell Tissue Res 244:63–67Google Scholar
  93. 93.
    Gabbiani G, Majno G (1972) Dupuytren's contracture: Fibroblast contraction? An ultrastructural study. Am J Pathol 66:131–146PubMedGoogle Scholar
  94. 94.
    Gabbiani G, Rungger-Brändle E (1981) The fibroblast. In: Glynn LE (ed) Handbook of inflammation: Tissue repair and regeneration. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 1–50Google Scholar
  95. 95.
    Gabbiani G, Ryan GB, Majno G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27:549–550Google Scholar
  96. 96.
    Gabbiani G, Chaponnier C, Hüttner I (1978) Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol 7:561–568Google Scholar
  97. 97.
    Gabbiani G, Schmid E, Winter S, Chaponnier C, de Chastonay C, Vanderkerckhove J, Weber K, Franke WW (1981) Vascular smooth muscle cells differ from other smooth muscle cells: Predominance of vimentin filaments and a specific α-type actin. Proc Natl Acad Sci USA 78:298–302Google Scholar
  98. 98.
    Galli SJ (1990) New insights into “the riddle of the mast cells”: Microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest 62:5–33Google Scholar
  99. 99.
    Garana RM, Petroll WM, Chen WT, Herman JM, Barry P, Andrews P, Cavanagh HD, Jester JV (1992) Radial keratomy. II. Role of the myofibroblast in corneal wound contraction. Invest Ophthalmol Vis Sci 33:3271–3282Google Scholar
  100. 100.
    Gard DL, Bell PB, Lazarides E (1979) Coexistence of desmin and the fibroblastic intermediate filament subunit in muscle and nonmuscle cells: Identification and comparative peptide analysis. Proc Natl Acad Sci USA 76:3894–3898Google Scholar
  101. 101.
    Garrels JI, Gibson W (1976) Identification and characterization of multiple forms of actin. Cell 9:793–805Google Scholar
  102. 102.
    Giuriato L, Scatena M, Chiavegato A, Tonello M, Scannapieco G, Pauletto P, Sartore S (1992) Non-muscle myosin isoforms and cell heterogeneity in developing rabbit vascular smooth muscle. J Cell Sci 101:233–246Google Scholar
  103. 103.
    Glasser SR, Julian J (1986) Intermediate filament protein as a marker of uterine stromal cell decidualization. Biol Reprod 35:463–474Google Scholar
  104. 104.
    Goldman RD, Lazarides E, Pollack R, Weber K (1975) The distribution of actin in nonmuscle cells. The use of actin antibody in the localization of actin within the microfilament bundles of mouse 3T3 cells. Exp Cell Res 90:333–344Google Scholar
  105. 105.
    Goldring SR, Stephenson ML, Downie E, Krane SM, Korn JH (1990) Heterogeneity in hormone responses and patterns of collagen synthesis in cloned dermal fibroblasts. J Clin Invest 85:798–803Google Scholar
  106. 106.
    Gorgas K, Böck P (1974) Myofibroblasts in the rat testicular capsule. Cell Tissue Res 154:533–541Google Scholar
  107. 107.
    Gown AM, Vogel AM, Gordon D, Lu PL (1985) A smooth muscle-specific monoclonal antibody recognizes smooth muscle actin isozymes. J Cell Biol 100:807–813Google Scholar
  108. 108.
    Grandstein RD, Murphy GF, Margolis RJ, Byrne MH, Amento EP (1987) Gamma-interferon inhibits collagen synthesis in vivo in the mouse. J Clin Invest 79:1254–1258Google Scholar
  109. 109.
    Grandstein RD, Rook A, Flotte TJ, Hass A, Gallo RL, Jaffe HS, Amento EP (1990) A controlled trial of intralesional recombinant interferon-γ in the treatment of keloidal scarring. Arch Dermatol 126:1295–1302Google Scholar
  110. 110.
    Greenhalgh DG, Sprugel KH, Murray MJ, Ross R (1990) PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 136:1235–1246Google Scholar
  111. 111.
    Gressner AM (1991) Beta-d-xyloside induced modulation of glycosaminoglycans, proliferation, and cytoskeletal organizations of rat liver myofibroblast-like cells (transformed fat storing cells). Cell Mol Biol 37:549–564Google Scholar
  112. 112.
    Grillo HC (1963) Origin of fibroblasts in wound healing: an autoradiographic study of inhibition of cellular proliferation by local X-irradiation. Ann Surg 157:453–467Google Scholar
  113. 113.
    Güldner FH, Wolff JR, Keyserlink D (1972) Fibroblasts as part of the contractile system in duodenal villi of rat. Z Zellforsch 135:349–360PubMedGoogle Scholar
  114. 114.
    Hahn AWA, Resink TJ, Kern F, Bühler FR (1992) Effects of endothelin-1 on vascular smooth muscle cell phenotypic differentiation. J Cardiovasc Pharmacol 20 [Suppl 12]:533–536Google Scholar
  115. 115.
    Hansson GK, Jonasson L, Holm J, Clowes MM, Clowes AW (1988) γ-Interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro. Circ Res 63:712–719Google Scholar
  116. 116.
    Hansson GK, Hellstrand M, Rymo L, Rubbia L, Gabbiani G (1989) Interferon-γ inhibits both proliferation and expression of differentiation-specific α-smooth muscle actin in arterial smooth muscle cells. J Exp Med 170:1595–1608Google Scholar
  117. 117.
    Harris AK, Stopack D, Wild P (1981) Fibroblast traction as a mechanism for collagen morphogenesis. Nature 290:249–251Google Scholar
  118. 118.
    Hasegawa T, Hirose T, Kudo E, Abe J, Hizawa K (1990) Cytoskeletal characteristics of myofibroblasts in benign and reactive fibroblastic lesions. Virchows Arch [A] 6:375–382Google Scholar
  119. 119.
    Heldin CH, Backstrom G, Ostman A, Hammacher A, Ronnstrand L, Rubin K, Nister M, Westermark B (1988) Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. EMBO J 7:1387–1394Google Scholar
  120. 120.
    Hennessey ES, Drummond DR, Sparrow JC (1993) Molecular genetics of actin function. Biochem J 282:657–671Google Scholar
  121. 121.
    Hoffmann-Beerling H (1954) Adenosintrophosphat als Betriestoff von Zellbewegungen. Biochim Biophys Acta 14:182–194Google Scholar
  122. 122.
    Hoover RL, Rosenberg R, Hearing W, Karnovsky MJ (1980) Inhibition of rat arterial smooth muscle cell proliferation by heparin. Circ Res 47:578–583Google Scholar
  123. 123.
    Hosang M (1988) Recombinant interferon-γ inhibits the mitogenic effect of platelet-derived growth factor at a level distal to the growth factor receptor. J Cell Physiol 134:396–404Google Scholar
  124. 124.
    Hunninghake GW, Hemkin C, Brady M, Monick M (1986) Immune interferon is a growth factor for human lung fibroblasts. Am Rev Respir Dis 134:1025–1028Google Scholar
  125. 125.
    Hurum S, Sodek J, Aubin JE (1982) Synthesis of collagen, collagenase and collagenase inhibitors by cloned human gingival fibroblasts and the effect of concanavalin A. Biochem Biophys Res Commun 107:357–366Google Scholar
  126. 126.
    Iezzoni JC, Mills SE (1993) Sarcomatoid carcinomas (carcinosarcomas) of the gastrointestinal tract: A review. Semin Diagn Pathol 10:176–187Google Scholar
  127. 127.
    Irle C, Kocher O, Gabbiani G (1980) Contractility of myofibroblasts during experimental liver cirrhosis. J Submicrosc Cytol 12:209–217Google Scholar
  128. 128.
    Janssen P (1902) Zur Lehre von der Dupuytren'schen Fingerkontraktur mit besondere Berücksichtigung der operativen Beseitigung und der pathologischen Anatomie des Leidens. Arch Klin Chir [Am] 67:761–789Google Scholar
  129. 129.
    Jester JV, Rodrigues MM, Herman JM (1987) Characterization of avascular corneal wound healing fibroblasts. New insights into the myofibroblast. Am J Pathol 127:140–148Google Scholar
  130. 130.
    Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzl P, Gordon K, Gown G (1991) Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. α-Smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest 87:847–858PubMedGoogle Scholar
  131. 131.
    Jonasson L, Holm J, Skalli O, Gabbiani G, Hansson GK (1985) Expression of class II transplantation antigen on vascular smooth muscle cells in human atherosclerosis. J Clin Invest 76:125–131Google Scholar
  132. 132.
    Jones JT, Jagelman DG, Fazio VW (1986) Desmoid tumors in familial polyposis. Ann Surg 204:94–97Google Scholar
  133. 133.
    Jordana M, Schulman J, Mcsharry C, Irving LB, Newhouse MT, Jordana G, Gauldie J (1988) Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue. Am Rev Respir Dis 137:579–584Google Scholar
  134. 134.
    Joyce NC, Haire MF, Palade GE (1987) Morphologic and biochemical evidence for a contractile cell network within the rat intestinal mucosa. Gastroenterology 92:68–81PubMedGoogle Scholar
  135. 135.
    Juliano RL, Haskill S (1993) Signal transduction from the extracellular matrix. J Cell Biol 120:577–585Google Scholar
  136. 136.
    Kampik A, Kenyon KR, Michels RG, Green WR, de la Cruz CZ (1981) Epiretinal and vitreous membranes. Comparative study of 56 cases. Arch Ophthalmol 99:1445–1454Google Scholar
  137. 137.
    Kapanci Y, Assimacopoulos A, Irlé C, Zwahlen A, Gabbiani G (1974) “Contractile interstitial cells” in pulmonary septa. J Cell Biol 60:375–392Google Scholar
  138. 138.
    Kapanci Y, Burgan S, Pietra GG, Conne B, Gabbiani G (1990) Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol 136:881–889Google Scholar
  139. 139.
    Kapanci Y, Ribaux C, Chaponnier C, Gabbiani G (1992) Cytoskeletal features of alveolar myofibroblasts and pericytes in normal human and rat lung. J Histochem Cytochem 40:1995–1963Google Scholar
  140. 140.
    Kaye GI, Lane N, Pascal PR (1968) Colonic pericryptal fibroblast sheath: replication, migration and cytodifferentiation of a mesenchymal cell-system in adult tissue. II. Fine structural aspects of normal rabbit and human colon. Gastroenterology 54:852–865Google Scholar
  141. 141.
    Khalil N, Bereznay O, Sporn M, Greenberg AH (1989) Macrophage production of transforming growth factor β and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med 170:727–737Google Scholar
  142. 142.
    Kocher O, Gabbiani G (1987) Analysis of α-smooth-muscle actin mRNA expression in rat aortic smooth-muscle cells using a specific cDNA probe. Differentiation 34:201–209Google Scholar
  143. 143.
    Kocher O, Skalli O, Bloom WS, Gabbiani G (1984) Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening. Lab Invest 50:645–652Google Scholar
  144. 144.
    Komuro T (1990) Re-evaluation of fibroblasts and fibroblast-like cells. Anat Embryol 182:103–112CrossRefPubMedGoogle Scholar
  145. 145.
    Korn JH (1985) Substrain heterogeneity in prostaglandin E2 synthesis of human dermal fibroblasts. Arthritis Rheum 28:315–322Google Scholar
  146. 146.
    Korn JH, Downie E (1989) Clonal interactions in fibroblast proliferation: Recognition of self vs. non-self. J Cell Physiol 141:437–440Google Scholar
  147. 147.
    Korn JH, Torres D, Downie E (1984) Clonal heterogeneity in the fibroblast response to mononuclear cell derived mediators. Arthritis Rheum 27:174–179Google Scholar
  148. 148.
    Kovacs EJ (1991) Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today 12:17–23Google Scholar
  149. 149.
    Kovilur S, Jacobson JW, Beach RL, Jeffery WR, Tomlinson C (1993) Evolution of the chordate muscle actin gene. J Mol Evol 36:361–368Google Scholar
  150. 150.
    Kuhn C, McDonald JA (1991) The roles of the myofibroblast in idiopathic pulmonary fibrosis. Am J Pathol 138:1257–1265Google Scholar
  151. 151.
    Lang RA, Metcalf D, Cuthbertson RA, Lyons I, Stanley E, Kelso A, Kannourakis G, Williamson DJ, Klintworth GK, Gonda TJ, Dunn AR (1987) Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell 51:675–686Google Scholar
  152. 152.
    Lantz M, Thysell H, Nilsson E, Olsson I (1991) On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin. J Clin Invest 88:2026–2031Google Scholar
  153. 153.
    Larjava H, Heino J, Krusius T, Vuorio E, Tammi M (1988) The small dermatan sulfate proteoglycans synthesized by fibroblasts derived from skin, synovium and gingiva show tissue-related heterogeneity. Biochem J 256:35–40Google Scholar
  154. 154.
    Larsen RD, Posch JL (1958) Dupuytren's contracture. With special reference to pathology. J Bone Joint Surg [Am] 40A:773–792Google Scholar
  155. 155.
    Lazarides E (1975) Tropomyosin antibody: The specific localization of tropomyosin in nonmuscle cells. J Cell Biol 65:549–561Google Scholar
  156. 156.
    Lazarides E, Burridge K (1975) Alpha-actinin: immunofluorescent localization of a muscle structural protein in nonmuscle cells. Cell 6:289–298Google Scholar
  157. 157.
    Leavitt J, Gunning P, Kedes L, Jariwalla R (1985) Smooth muscle α-actin is a transformation-sensitive marker for mouse NIH 3T3 and rat-2 cells. Nature 316:840–842Google Scholar
  158. 158.
    Levi-Schaffer F, Austen KF, Caulfield JP, Hein A, Bloes WF, Stevens RL (1985) Fibroblasts maintain the phenotype and viability of the rat heparin-containing mast cells in vitro. J Immunol 135:3454–3462Google Scholar
  159. 159.
    Liesveld JL, Abboud CN, Duerst RE, Ryan DH, Brennan JK, Lichtman MA (1989) Characterization of human marrow stromal cells: role in progenitor cell binding and granulopoiesis. Blood 73:1793–1800Google Scholar
  160. 160.
    Limeback H, Sodek J, Aubin JE (1982) Variation in collagen expression by cloned periodontal ligament cells. J Periodont Res 18:242–248Google Scholar
  161. 161.
    Liotta LA, Steeg PS, Stettler-Stevenson G (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336Google Scholar
  162. 162.
    Lynch SE, Nixon JC, Colvin RB, Antoniades HN (1987) Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci USA 84:7696–7700Google Scholar
  163. 163.
    MacDonald RA (1959) Origin of fibroblasts in experimental healing wounds: autoradiographic studies using tritiated thymidine. Surgery 46:376–382Google Scholar
  164. 164.
    Macieira-Coelho A (1988) Biology of normal proliferating cells in vitro. Relevance for in vivo aging. In: von Hahn HP (ed) Interdisciplinary topics in gerontology, vol 23, Karger, BaselGoogle Scholar
  165. 165.
    Macieira-Coelho A, Taboury F (1982) A re-evaluation of the changes in proliferation in human fibroblasts during ageing in vitro. Cell Tissue Kinet 15:213–224Google Scholar
  166. 166.
    MacNulty EE, Plevin R, Wakelam MJO (1990) Stimulation of the hydrolysis of phosphatidylinositol 4,5-biphosphate and phosphatidylcholine by endothelin, a complete mitogen for Rat-1 fibroblasts. Biochem J 272:761–766Google Scholar
  167. 167.
    Madri JA, Carter D (1984) Scar cancer of the lung: origin and significance. Hum Pathol 15:625–631Google Scholar
  168. 168.
    Majack RA, Bornstein P (1984) Heparin and related glycosaminoglycans modulate the secretory phenotype of vascular smooth muscle cells. J Cell Biol 99:1688–1695Google Scholar
  169. 169.
    Majno G, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine-like mediators. An electron microscopic study. J Cell Biol 42:647–672Google Scholar
  170. 170.
    Martin GM, Sprague CA, Norwood TH, Pendergrass WR (1974) Clonal selection, attenuation and differentiation in an in vitro model of hyperplasia. Am J Pathol 74:137–154Google Scholar
  171. 171.
    Martin P, Hopkinson-Woolley J, McCluskey J (1992) Growth factors and cutaneous wound repair. Prog Growth Factor Res 4:25–44Google Scholar
  172. 172.
    Massagué J (1992) Receptors for the TGF-β family. Cell 69:1067–1070Google Scholar
  173. 173.
    Matsuoka M, Pham NT, Tsukamato H (1989) Differential effects of interleukin 1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured rat-storing cells. Liver 9:71–78Google Scholar
  174. 174.
    McCaffrey TA, Falcone DJ, Brayton CF, Agarwal LA, Welt FGP, Weksler BB (1989) Transforming growth factor-β activity is potentiated by heparin via dissociation of the transforming growth factor-β/α2-macroglobulin inactive complex. J Cell Biol 109:441–448Google Scholar
  175. 175.
    McCaffrey TA, Falcone DJ, Du B (1992) Transforming growth factor-β1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-β1. J Cell Physiol 152:430–440Google Scholar
  176. 176.
    McCulloch CAG, Bordin S (1991) Role of fibroblast subpopulations in periodontal physiology and pathology. J Periodont Res 26:144–154Google Scholar
  177. 177.
    Melin M, Hartmann DJ, Magloire H, Falcoff E, Auriault C, Grimaud JA (1989) Human recombinant gamma-interferon stimulates proliferation and inhibits collagen and fibronectin production by human dental pulp fibroblasts. Cell Mol Biol 35:97–110Google Scholar
  178. 178.
    Mitchell JJ, Woodcock-Mitchell J, Reynolds S, Low R, Leslie K, Adler K, Gabbiani G, Skalli O (1989) α-Smooth muscle actin in parenchymal cells of bleomycin-injured rat lung. Lab Invest 60:643–650Google Scholar
  179. 179.
    Mooseker M (1993) A multitude of myosin. Curr Biol 3:245–248Google Scholar
  180. 180.
    Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factor-β. Science 237:1333–1336Google Scholar
  181. 181.
    Mustoe TA, Pierce GF, Morishima C, Deuel TF (1991) Gowith factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 87:694–703Google Scholar
  182. 182.
    Muthukrishnan L, Warder E, McNeil PL (1991) Basic fibroblast growth factor is efficiently released from a cytosolic storage site through plasma membrane disruptions of endothelial cells. J Cell Physiol 148:1–16Google Scholar
  183. 183.
    Narayanan AS, Page RC (1983) Byosynthesis and regulation of type V collagen in diploid human fibroblasts. J Biol Chem 258:11694–11699Google Scholar
  184. 184.
    Narayanan AS, Page RC, Swanson J (1989) Collagen synthesis by human fibroblasts. Regulation by transforming growth factor-β in the presence of other inflammatory mediators. Biochem J 260:463–469Google Scholar
  185. 185.
    Nouchi T, Tanaka Y, Tsukada T, Sato C, Marumo F (1991) Appearance of alpha-smooth muscle-actin positive cells in hepatic fibrosis. Liver 11:100–105Google Scholar
  186. 186.
    Nowotny GEK, Pau H (1984) Myofibroblast-like cells in human anterior capsular cataract. Virchows Arch [A] 404:393–401Google Scholar
  187. 187.
    Okomoto-Inoue M, Taniguchi S, Sadano H, Kawano T, Kimura G, Gabbiani G, Baba T (1990) Alteration of expression of smooth muscle α-actin associated with transformation of rat 3Y1 cells. J Cell Sci 96:631–637Google Scholar
  188. 188.
    Ornitz DM, Yayon A, Flanagan JG, Svahn CM, Levi E, Leder P (1992) Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol Cell Biol 12:240–247Google Scholar
  189. 189.
    Osborn M, Caselitz J, Weber K (1981) Heterogeneity of intermediate filament expression in vascular smooth muscle: a gradient in desmin positive cells from the rat aortic arch to the level of the arteria iliaca communis. Differentiation 20:196–202Google Scholar
  190. 190.
    O'Shea JD (1970) An ultrastructural study of smooth musclelike cells in the theca externa of the ovarian follicle of the rat. Anat Rec 167:127–131Google Scholar
  191. 191.
    Peled A, Zipori D, Abramsky O, Ovadia H, Shezen E (1991) Expression of α-smooth muscle actin in murine bone marrow stromal cells. Blood 78:304–309Google Scholar
  192. 192.
    Phipps RP, Penney DP, Keng P, Silvera M, Harkins S, Derdak S (1990) Immune functions of subpopulations of lung fibroblasts. Immunol Res 9:275–286Google Scholar
  193. 193.
    Pierce GF, Mustoe TA, Senior RM, Reed J, Griffin GL, Thomason A, Deuel TF (1988) In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins. J Exp Med 167:974–987Google Scholar
  194. 194.
    Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A (1991) Role of platelet-derived growth factor in would healing. J Cell Biochem 45:319–326Google Scholar
  195. 195.
    Pinkus GS, Warhol MJ, O'Connor EM, Etheridge CL, Fujiware K (1986) Immunohistochemical localization of smooth muscle moysin in human spleen, lymph node, and other lymphoid tissues. Am J Pathol 123:440–453Google Scholar
  196. 196.
    Pittet B, Rubbia-Brandt L, Desmoulière A, Sappino AP, Roggero P, Guerret S, Grimaud JA, Lacher R, Montandon D, Gabbiani G (1994) Effect of γ-Interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren's disease. Plast Reconstr Surg 93:1224–1235Google Scholar
  197. 197.
    Poulsom R, Pignatelli M, Stefler-Stevenson WG, Liotta LA, Wright PA, Jeffery RE, Longroft JM, Rogers L, Stamp GH (1992) Stromal expression of 72 kDa type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am J Pathol 141:389–396Google Scholar
  198. 198.
    Raats JMH, Bloemendal H (1992) The role of protein domains in the assembly process of intermediate filaments. Progr Nucleic Acid Res Mol Biol 43:57–86Google Scholar
  199. 199.
    Ramadori G (1991) The stellate cell (Ito-cell, fat-storing cell, lipocyte, perisinusoidal cell) of the liver. Virchows Arch [B] 61:147–158Google Scholar
  200. 200.
    Rangdaeng S, Truong LD (1991) Comparative immunohisto-chemical staining for desmin and muscle-specific actin. A study of 576 cases. Am J Clin Pathol 96:32–45Google Scholar
  201. 201.
    Rappolee DA, Mark D, Banda MJ, Werb Z (1988) Wound macrophages express TGF-α and other growth factors in vivo: analysis by mRNA phenotyping. Science 241:708–712Google Scholar
  202. 202.
    Rasbridge SA, Gillett CE, Millis RR (1993) Oestrogen and progesterone receptor expression in mammary fibromatosis. J Clin Pathol 46:349–351Google Scholar
  203. 203.
    Rifkin DB, Mostacelli D (1989) Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol 109:1–6Google Scholar
  204. 204.
    Robson MC (1991) Growth factors as wound healing agents. Curr Opin Biotech 2:863–867Google Scholar
  205. 205.
    Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF (1992) Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 339:23–25Google Scholar
  206. 206.
    Rodeman HP, Müller GA (1990) Abnormal growth, clonal proliferation and 35S-methionine polypeptide pattern of fibroblasts derived from kidneys with intersticial fibrosis. Proc Soc Exp Biol Med 195:57–63Google Scholar
  207. 207.
    Ronnov-Jessen L, van Durs B, Celis JE, Petersen OW (1990) Smooth muscle differentiation in cultured human breast gland stromal cells. Lab Invest 63:532–543Google Scholar
  208. 208.
    Ross R, Raines EW (1990) Platelet-derived growth factor and cell proliferation. In: Sara VR et al. (eds) Growth factors: from genes to clinical application. Raven Press, New York, pp 193–199Google Scholar
  209. 209.
    Ross R, Everett NB, Tyler R (1970) Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J Cell Biol 44:645–654Google Scholar
  210. 210.
    Rubbia-Brandt L, Sappino AP, Gabbiani G (1991) Locally applied GM-CSF induces the accumulation of α-smooth muscle actin containing myofibroblasts. Virchows Arch [B] 60:73–82Google Scholar
  211. 211.
    Rubenstein AP (1990) The functional importance of multiple actin isoforms. BioEssays 12:309–315Google Scholar
  212. 212.
    Rudolph R (1976) The effect of skin graft preparation on wound contraction. Surg Gynecol Obstet 142:49–56Google Scholar
  213. 213.
    Rudolph R, Vande Berg J (1991) The myofibroblast in Dupuytren's contracture. Hand Clin 7:683–692Google Scholar
  214. 214.
    Ruoslahti E, Yamaguchi Y (1991) Proteoglycans as modulators of growth factor activities. Cell 64:867–869CrossRefPubMedGoogle Scholar
  215. 215.
    Ryan GB, Cliff WJ, Gabbiani G, Irle C, Montandon D, Statkov PR, Majno G (1974) Myofibroblasts in human granulation tissue. Hum Pathol 5:55–67Google Scholar
  216. 216.
    Sakakura T, Sakagami Y, Nishizuka Y (1979) Acceleration of mammary cancer development by grafting of fetal mammary mesenchymes in C3H mice. Gann 70:459–466Google Scholar
  217. 217.
    Sappino AP, Skalli O, Jackson B, Schürch W, Gabbiani G (1988) Smooth-muscle differentiation in stromal of malignant and non-malignant breast tissues. Int J Cancer 41:707–712Google Scholar
  218. 218.
    Sappino AP, Dietrich PY, Widgren S, Gabbiani G (1989) Colonic pericryptal fibroblasts. Differentiation pattern in embryogenesis and phenotypic modulation in epithelial proliferative lesions. Virchows Arch [A] 415:551–557Google Scholar
  219. 219.
    Sappino AP, Massouyé I, Saurat JH, Gabbiani G (1990) Smooth muscle differentiation in scleroderma fibroblastic cells. Am J Pathol 137:585–591Google Scholar
  220. 220.
    Sappino AP, Schürch W, Gabbiani G (1990) Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63:144–161Google Scholar
  221. 221.
    Schmitt-Gräff A, Borchard F (1992) Cardiac myxoma with a cytoskeratin-immunoreactive glandular component. Pathol Res Pract 188:217–221Google Scholar
  222. 222.
    Schmitt-Gräff A, Gabbiani G (1992) Phenotypic features of stromal cells in normal, premalignant and malignant conditions. Eur J Cancer 28A:1916–1920Google Scholar
  223. 223.
    Schmitt-Gräff A, Skalli O, Gabbiani G (1989) α-Smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions. Virchows Arch [B] 57:291–302Google Scholar
  224. 224.
    Schmitt-Gräff A, Pau H, Spahr R, Piper M, Skalli O, Gabbiani G (1990) Appearance of alpha-smooth muscle actin in human eye lens cells of anterior capsular cataract in cultured bovine lens-forming cells. Differentiation 43:115–122Google Scholar
  225. 225.
    Schmitt-Gräff A, Krüger S, Bochard F, Gabbiani G, Denk H (1991) Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol 138:1233–1242Google Scholar
  226. 226.
    Schmitt-Gräff A, Chakroun G, Gabbiani G (1993) Modulation of perisinusoidal cell cytoskeletal features during experimental hepatic fibrosis. Virchows Arch [A] 422:99–107Google Scholar
  227. 227.
    Schürch W, Seemayer TA, Gabbiani G (1992) Myofibroblast. In: Sternberg SS (ed) Histology for pathologists. Raven Press, New York, pp 109–144Google Scholar
  228. 228.
    Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, Bowen-Pope DF (1989) Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem 264:8771–8778Google Scholar
  229. 229.
    Shah M, Foreman DM, Ferguson MWJ (1992) Control of scarring in adult wounds by neutralising antibody to transforming growth factor β. Lancet 339:213–214CrossRefPubMedGoogle Scholar
  230. 230.
    Shepherd JP, Dawber RPR (1984) Wound healing and scarring after cryosurgery. Cryobiol 21:157–169Google Scholar
  231. 231.
    Shimizu K, Yoshizato K (1992) Organ-dependent expression of differentiated states in fibroblasts cultured in vitro. Dev Growth Differen 34:43–50Google Scholar
  232. 232.
    Shum DT, McFarlane RM (1988) Histogenesis-of Dupuytren's disease: an immunohistochemical study of 30 cases. J Hand Surg 13A:61–67Google Scholar
  233. 233.
    Singer II (1979) The fibronexus: a transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts. Cell 16:675–685Google Scholar
  234. 234.
    Singer II, Kawka DW, Kazazis DM, Clark RAF (1984) In vivo co-distribution of fibronectin and actin fibers in granulation tissue: Immunofluorescence and electron microscope studies of the fibronexus at the myofibroblast surface. J Cell Biol 98:2091–2106Google Scholar
  235. 235.
    Skalli O, Gabbiani G (1988) The biology of the myofibroblast. Relationship to wound contraction and fibrocontractive diseases. In: Clark RAF, Henson PM (eds) The molecular and cellular biology of wound repair. Plenum, New York, pp 373–402Google Scholar
  236. 236.
    Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol 103:2787–2796Google Scholar
  237. 237.
    Skalli O, Gabbiani G, Babaï F, Seemayer TA, Schürch W (1988) Intermediate filament proteins and actin isoforms as markers for soft tissue tumor differentiation and origin. II. Rhabdomyosarcomas. Am J Pathol 139:515–531Google Scholar
  238. 238.
    Skalli O, Schürch W, Seemayer TA, Lagacé R, Montandon D, Pittet B, Gabbiani G (1989) Myofibroblasts from diverse pathological settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest 60:275–285Google Scholar
  239. 239.
    Smith JR, Hayflick L (1974) Variation in the life-span of clones derived from human diploid cell strains. J Cell Biol 62:48–53Google Scholar
  240. 240.
    Sporn MB, Roberts A (1992) Transforming growth factor-β: recent progress and new challenges. J Cell Biol 119:1017–1021Google Scholar
  241. 241.
    Stiller D, Katenkamp D (1975) Cellular features in desmoid fibromatosis and well-differentiated fibrosarcomas, an electron microscopic study. Virchows Arch [A] 369:155–164Google Scholar
  242. 242.
    Streuli CH, Schmidhauser C, Kobrin M, Bissell MJ, Derynck R (1993) Extracellular matrix regulates expression of the TGF-β1 gene. J Cell Biol 120:253–260Google Scholar
  243. 243.
    Tabone E, Andujar MB, De Barros SS, Dos Santos MN, BarrosCL, Graça DL (1983) Myofibroblast-like cells in non-pathological bovine endometrial caruncle. Cell Biol Int Rep 7:395–400Google Scholar
  244. 244.
    Tagaki M, Yamamoto H, Megatt, Hsieh KJ, Shioda S, Enamoto S (1991) Heterogeneity in the gingival fibromatoses. Cancer 68:2202–2212Google Scholar
  245. 245.
    Tan-Liu NS, Matsubara O, Grillo HC, Marc EJ (1989) Invasive fibrous tumor of the tracheobronchial tree: clinical and pathologic study of seven cases. Hum Pathol 20:180–184Google Scholar
  246. 246.
    Thiemermann C, Corder R (1992) Is endothelin-1 the regulator of myofibroblast contraction during wound healing? Lab Invest 67:677–679Google Scholar
  247. 247.
    Thomas KA (1987) Fibroblast growth factors. FASEB J 1:434–440Google Scholar
  248. 248.
    Toccanier-Pelte MF, Skalli O, Kapanci Y, Gabbiani G (1987) Characterization of stromal cells with myoid features in lymph nodes and spleen in normal and pathologic conditions. Am J Pathol 129:109–118Google Scholar
  249. 249.
    Tsukada T, McNutt MA, Ross R, Gown AM (1987) HHF35, a muscle actin-specific monoclonal antibody. II. Reactivity in normal, reactive, and neoplastic human tissues. Am J Pathol 127:389–402Google Scholar
  250. 250.
    Tsukamato H, Mishima Y, Hayashibe K, Sasase H (1992) α-Smooth muscle actin expression in tumor and stromal cells of benign and malignant human pigment cell tumors. J Invest Dermatol 98:116–120Google Scholar
  251. 251.
    Van den Hooff A (1988) Stromal involvement in malignant growth. Adv Cancer Res 50:159–196Google Scholar
  252. 252.
    Vande Berg JS, Rudolph R (1985) Cultured myofibroblasts: a useful model to study wound contraction and pathological contracture. Ann Plast Surg 14:111–120Google Scholar
  253. 253.
    Vande Berg JS, Rudolph R, Woodward M (1984) Comparative growth dynamics and morphology between cultured myofibroblasts from granulating wounds and dermal fibroblasts. Am J Pathol 114:187–200Google Scholar
  254. 254.
    Vandekerckhove J, Weber K (1978) At least six different actins are expressed in higher mammals: an analysis based on the amino acid sequence of the amino terminal tryptic peptide. J Mol Biol 126:783–802Google Scholar
  255. 255.
    Vyalov S, Desmoulière A, Gabbiani G (1993) GM-CSF-induced granulation tissue formation: relationships between macrophage and myofibroblast accumulation. Virchows Arch [B] 63:231–239Google Scholar
  256. 256.
    Vyalov SL, Gabbiani G, Kapanci Y (1993) Rat alveolar myofibroblasts acquire α-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis. Am J Pathol 63:231–239Google Scholar
  257. 257.
    Wang K (1977) Filamin, a new high-molecular-weight protein found in smooth muscle and nonmuscle cells. Purification and properties of chicken gizzard filamin. Biochemistry 16:1857–1865Google Scholar
  258. 258.
    Weber K, Groeschel-Stewart U (1974) Antibody to myosin: the specific visualization of myosin-containing filaments in nonmuscle cells. J Cell Biol 71:4561–4564Google Scholar
  259. 259.
    Weich HA, Salahuddin SZ, Gill P, Nakamura S, Gallo R, Folkmann J (1991) AIDS-associated Kaposi's Sarcoma-derived cells in long-term culture express and synthesize smooth muscle alpha-actin. Am J Pathol 139:1251–1258Google Scholar
  260. 260.
    Weiss SW, Langloss JM, Shmookler BM (1986) Estrogen receptor protein in bone and soft tissue tumors. Lab Invest 54:689–694Google Scholar
  261. 261.
    Whiteside TL, Ferrarini M, Hebda P, Buckingham RB (1988) Heterogeneous symthetic phenotype of cloned scleroderma fibroblasts may be due to aberrant regulation in the synthesis of connective tissues. Arthritis Rheum 31:1221–1229Google Scholar
  262. 262.
    Wick MR, Swanson PE (1993) Carcinosarcomas: current perspectives and historical review of nosological concepts. Semm Diagn Pathol 10:118–127Google Scholar
  263. 263.
    Wight TN (1989) Cell biology of arterial proteoglycans. Arteriosclerosis 9:1–20Google Scholar
  264. 264.
    Willingham MC, Yamada SS, Davies PJA, Rutherford AV, Gallo MG, Pastan I (1981) Intracellular localization of actin in cultured fibroblasts by electron microscopic immunochemistryy. J Histochem Cytochem 29:17–37Google Scholar
  265. 265.
    Yamakage A, Kukuchi K, Smith EA, LeRoy EC, Trojanowska M (1992) Selective upregulation of platelet-derived growth factor β receptors by transforming growth factor β in scleroderma fibroblasts. J Exp Med 175:1227–1234Google Scholar
  266. 266.
    Yamasaki A, Rose GG, Pinero GJ, Mahan CJ (1987) Microfilaments in human cementoblasts and periodontal fibroblasts. J Periodontol 58:40–45Google Scholar
  267. 267.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415CrossRefPubMedGoogle Scholar
  268. 268.
    Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM (1991) Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64:841–848Google Scholar
  269. 269.
    Yokoi Y, Namihisa T, Kuroda H, Komatsu I, Miyazaki A, Watanabe S, Usui K (1984) Immunocytochemical detection of desmin in fat-storing cells (Ito cells). Hepatology 4:709–714Google Scholar
  270. 270.
    Zavala C, Herner G, Fialkow PJ (1978) Evidence for selection in cultured diploid fibroblast strains. Exp Cell Res 117:137–144Google Scholar

Copyright information

© Springer Verlag 1994

Authors and Affiliations

  • Annette Schmitt-Gräff
    • 1
  • Alexis Desmoulière
    • 1
  • G. Gabbiani
    • 1
  • A. Schmitt-Gräff
    • 2
  • A. Desmoulière
    • 3
  1. 1.Department of PathologyCentre Médical UniversitaireGeneva 4Switzerland
  2. 2.Institut für PathologieUniversitätsklinikum Steglitz, Freie Universität BerlinBerlin 45Germany
  3. 3.Institut Pasteur de LyonCNRS-URA 1459Lyon Cedex 7France

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