Epithelial Repair and Regeneration

  • Steven L. Brody
  • Jeffrey J. Atkinson
Part of the Molecular Pathology Library book series (MPLB, volume 1)

Abstract

Contact with the environment positions the respiratory epithelium at risk for acute and chronic injury from infectious pathogens, noxious agents, and inflammatory processes. Thus, to protect gas transfer within the lung the epithelium is programmed for routine maintenance and repair. Programs for repair are directed by epithelial, mesenchymal, and inflammatory signals that collectively constitute highly regulated networks. Principal components of the repair network are developmental morphogens, integrin and growth factor signaling molecules, and transcription factors. The epithelium responds to these signals with a remarkable plasticity and is bulwarked by a population of lung progenitor cells to ensure maintenance and repair for fluid balance and host defense functions.

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References

  1. 1.
    Kauffman SL. Cell proliferation in the mammalian lung. Int Rev Exp Pathol 1980;22:131–191.PubMedGoogle Scholar
  2. 2.
    Enesco M, Leblond CP. Increase in cell number as a factor in the growth of the young male rat. J Embryol Exp Morphol 1962;10:530–562.Google Scholar
  3. 3.
    Kauffman SL. Alteration in cell proliferation in mouse lung following urethane exposure. II. Effects of chronic exposure on terminal bronchiolar epithelium. Am J Pathol 1971;64(3):531–538.PubMedGoogle Scholar
  4. 4.
    Cameron IL. Cell renewal in the organs and tissues of the nongrowing adult mouse. Tex Rep Biol Med 1970;28(3):203–248.PubMedGoogle Scholar
  5. 5.
    Simnett JD, Heppleston AG. Cell renewal in the mouse lung. The influence of sex, strain, and age. Lab Invest 1966;15(11):1793–1801.PubMedGoogle Scholar
  6. 6.
    Clark RAF. The Molecular and Cellular Biology of Wound Repair, 2nd ed. New York: Plenum Press; 1996.Google Scholar
  7. 7.
    Wilhelm DL. Regeneration of tracheal epithelium. J Pathol Bacteriol 1953;65(2):543–550.PubMedGoogle Scholar
  8. 8.
    Erjefalt JS, Erjefalt I, Sundler F, Persson CG. In vivo restitution of airway epithelium. Cell Tissue Res 1995;281(2):305–316.PubMedGoogle Scholar
  9. 9.
    Keenan KP, Combs JW, McDowell EM. Regeneration of hamster tracheal epithelium after mechanical injury. I. Focal lesions: quantitative morphologic study of cell proliferation. Virchows Arch B Cell Pathol Incl Mol Pathol 1982;41(3):193–214.PubMedGoogle Scholar
  10. 10.
    Lane BP, Gordon R. Regeneration of rat tracheal epithelium after mechanical injury. I. The relationship between mitotic activity and cellular differentiation. Proc Soc Exp Biol Med 1974;145(4):1139–1144.PubMedGoogle Scholar
  11. 11.
    Gordon RE, Lane BP. Regeneration of rat tracheal epithelium after mechanical injury. II. Restoration of surface integrity during the early hours after injury. Am Rev Respir Dis 1976;113(6):799–807.PubMedGoogle Scholar
  12. 12.
    Rickard KA, Taylor J, Rennard SI, Spurzem JR. Migration of bovine bronchial epithelial cells to extracellular matrix components. Am J Respir Cell Mol Biol 1993;8(1):63–68.PubMedGoogle Scholar
  13. 13.
    Shimizu T, Nishihara M, Kawaguchi S, Sakakura Y. Expression of phenotypic markers during regeneration of rat tracheal epithelium following mechanical injury. Am J Respir Cell Mol Biol 1994;11(1):85–94.PubMedGoogle Scholar
  14. 14.
    Zahm JM, Chevillard M, Puchelle E. Wound repair of human surface respiratory epithelium. Am J Respir Cell Mol Biol 1991;5(3):242–248.PubMedGoogle Scholar
  15. 15.
    Kheradmand F, Folkesson HG, Shum L, et al. Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model. Am J Physiol 1994;267(6 Pt 1):L728–L738.PubMedGoogle Scholar
  16. 16.
    Lawson GW, Van Winkle LS, Toskala E, et al. Mouse strain modulates the role of the ciliated cell in acute tracheobronchial airway injury—distal airways. Am J Pathol 2002;160(1):315–327.PubMedGoogle Scholar
  17. 17.
    Look DC, Walter MJ, Williamson MR, et al. Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function. Am J Pathol 2001;159(6):2055–2069.PubMedGoogle Scholar
  18. 18.
    Adamson IY, Bowden DH. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest 1974;30(1):35–42.PubMedGoogle Scholar
  19. 19.
    Sannes PL, Burch KK, Khosla J, et al. Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs. Am J Respir Cell Mol Biol 1993;8(3):245–251.PubMedGoogle Scholar
  20. 20.
    Yurchenco PD, Amenta PS, Patton BL. Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol 2004;22(7):521–538.PubMedGoogle Scholar
  21. 21.
    McGowan SE. Extracellular matrix and the regulation of lung development and repair. FASEB J 1992;6(11):2895–2904.PubMedGoogle Scholar
  22. 22.
    Tomashefski JF Jr. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 2000;21(3):435–466.PubMedGoogle Scholar
  23. 23.
    Wesselkamper SC, Case LM, Henning LN, et al. Gene expression changes during the development of acute lung injury: role of transforming growth factor beta. Am J Respir Crit Care Med 2005;172(11):1399–1411.PubMedGoogle Scholar
  24. 24.
    Rosi E, Beckmann JD, Pladsen P, et al. Modulation of human bronchial epithelial cell IIICS fibronectin mRNA in vitro. Eur Respir J 1996;9(3):549–555.PubMedGoogle Scholar
  25. 25.
    Greiling D, Clark RA. Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix. J Cell Sci 1997;110(Pt 7):861–870.PubMedGoogle Scholar
  26. 26.
    Hocking DC, Chang CH. Fibronectin matrix polymerization regulates small airway epithelial cell migration. Am J Physiol Lung Cell Mol Physiol 2003;285(1):L169–L179.PubMedGoogle Scholar
  27. 27.
    Sheppard D. Functions of pulmonary epithelial integrins: from development to disease. Physiol Rev 2003;83(3):673–686.PubMedGoogle Scholar
  28. 28.
    Kim HJ, Henke CA, Savik SK, Ingbar DH. Integrin mediation of alveolar epithelial cell migration on fibronectin and type I collagen. Am J Physiol 1997;273(1 Pt 1):L134–L41.PubMedGoogle Scholar
  29. 29.
    Laskin DL, Kimura T, Sakakibara S, et al. Chemotactic activity of collagen-like polypeptides for human peripheral blood neutrophils. J Leuk Biol 1986;39(3):255–266.Google Scholar
  30. 30.
    Li Q, Park PW, Wilson CL, Parks WC. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 2002;111(5):635–646.PubMedGoogle Scholar
  31. 31.
    Bonner JC. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 2004;15(4):255–273.PubMedGoogle Scholar
  32. 32.
    Clark RA. Fibrin is a many splendored thing. J Invest Dermatol 2003;121(5):XXI–XXII.PubMedGoogle Scholar
  33. 33.
    Van Leer C, Stutz M, Haeberli A, Geiser T. Urokinase plasminogen activator released by alveolar epithelial cells modulates alveolar epithelial repair in vitro. Thromb Haemost 2005;94(6):1257–1264.PubMedGoogle Scholar
  34. 34.
    Giangreco A, Reynolds SD, Stripp BR. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol 2002;161(1):173–182.PubMedGoogle Scholar
  35. 35.
    Hong Ku, Reynolds SD, Giangreco A, et al. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol 2001;24(6):671–681.PubMedGoogle Scholar
  36. 36.
    Seto ES, Bellen HJ. The ins and outs of Wingless signaling. Trends Cell Biol 2004;14(1):45–53.PubMedGoogle Scholar
  37. 37.
    Orsulic S, Huber O, Aberle H, et al. E-cadherin binding prevents beta-catenin nuclear localization and betacatenin/LEF-1-mediated transactivation. J Cell Sci 1999;112(Pt 8):1237–1245.PubMedGoogle Scholar
  38. 38.
    Park KS, Wells JM, Zorn AM, et al. Transdifferentiation of ciliated cells during repair of the respiratory epithelium. Am J Respir Cell Mol Biol 2006;34(2):151–157.PubMedGoogle Scholar
  39. 39.
    Oertel M, Graness A, Thim L, et al. Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor. Am J Respir Cell Mol Biol 2001;25(4):418–424.PubMedGoogle Scholar
  40. 40.
    Kim JS, McKinnis VS, Nawrocki A, White SR. Stimulation of migration and wound repair of guinea-pig airway epithelial cells in response to epidermal growth factor. Am J Respir Cell Mol Biol 1998;18(1):66–74.PubMedGoogle Scholar
  41. 41.
    Evans MJ, Stephens RJ, Freeman G. Effects of nitrogen dioxide on cell renewal in the rat lung. Arch Intern Med 1971;128(1):57–60.PubMedGoogle Scholar
  42. 42.
    Akiyama SK. Integrins in cell adhesion and signaling. Hum Cell 1996;9(3):181–186.PubMedGoogle Scholar
  43. 43.
    Pilewski JM, Latoche JD, Arcasoy SM, Albelda SM. Expression of integrin cell adhesion receptors during human airway epithelial repair in vivo. Am J Physiol 1997;273(1 Pt 1):L256–L263.PubMedGoogle Scholar
  44. 44.
    Clark RA, Lin F, Greiling D, et al. Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan. J Invest Dermatol 2004;122(2):266–277.PubMedGoogle Scholar
  45. 45.
    Lin F, Ren XD, Doris G, Clark RA. Three-dimensional migration of human adult dermal fibroblasts from collagen lattices into fibrin/fibronectin gels requires syndecan-4 proteoglycan. J Invest Dermatol 2005;124(5):906–913.PubMedGoogle Scholar
  46. 46.
    McGuire JK, Li Q, Parks WC. Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 2003;162(6):1831–1843.PubMedGoogle Scholar
  47. 47.
    Legrand C, Gilles C, Zahm JM, et al. Airway epithelial cell migration dynamics. MMP-9 role in cell-extracellular matrix remodeling. J Cell Biol 1999;146(2):517–529.PubMedGoogle Scholar
  48. 48.
    Legrand C, Polette M, Tournier JM, et al. UPA/plasmin system-mediated MMP-9 activation is implicated in bronchial epithelial cell migration. Exp Cell Res 2001;264(2):326–36.PubMedGoogle Scholar
  49. 49.
    Chen P, Farivar AS, Mulligan MS, Madtes DK. tissue inhibitor of metalloproteinase-1 deficiency abrogates obliterative airway disease after heterotopic tracheal transplantation. Am J Respir Cell Mol Biol 2006;34(4):464–472.PubMedGoogle Scholar
  50. 50.
    Chu EK, Cheng J, Foley JS, et al. Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells. Am J Respir Cell Mol Biol 2006;35(6):628–638.PubMedGoogle Scholar
  51. 51.
    Lazar MH, Christensen PJ, Du M, et al. Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin. Am J Respir Cell Mol Biol 2004;31(6):672–678.PubMedGoogle Scholar
  52. 52.
    Hotary KB, Yana I, Sabeh F, et al. Matrix metalloproteinases (MMPs) regulate fibrin-invasive activity via MT1-MMP-dependent and-independent processes. J Exp Med 2002;195(3):295–308.PubMedGoogle Scholar
  53. 53.
    Parks WC, Shapiro SD. Matrix metalloproteinases in lung biology. Respir Res 2001;2(1):10–19.PubMedGoogle Scholar
  54. 54.
    Hintermann E, Quaranta V. Epithelial cell motility on laminin-5: regulation by matrix assembly, proteolysis, integrins and ErbB receptors. Matrix Biol 2004;23(2):75–85.PubMedGoogle Scholar
  55. 55.
    De Giorgio-Miller A, Bottoms S, Laurent G, et al. Fibrininduced skin fibrosis in mice deficient in tissue plasminogen activator. Am J Pathol 2005;167(3):721–732.PubMedGoogle Scholar
  56. 56.
    Baker SE, Hopkinson SB, Fitchmun M, et al. Laminin-5 and hemidesmosomes: role of the alpha 3 chain subunit in hemidesmosome stability and assembly. J Cell Sci 1996;109(Pt 10):2509–2520.PubMedGoogle Scholar
  57. 57.
    Citri A, Yarden Y. EGF-ErbB Signalling: towards the systems level. Nat Rev Mol Cell Biol 2006;7(7):505–516.PubMedGoogle Scholar
  58. 58.
    Sheppard D. Transforming growth factor-beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc 2006;3(5):413–417.PubMedGoogle Scholar
  59. 59.
    Ware LB, Matthay MA. Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair. Am J Physiol Lung Cell Mol Physiol 2002;282(5):L924–L40.PubMedGoogle Scholar
  60. 60.
    Evans MJ, Johnson LV, Stephens RJ, Freeman G. Cell renewal in the lungs of rats exposed to low levels of ozone. Exp Mol Pathol 1976;24(1):70–83.PubMedGoogle Scholar
  61. 61.
    Bindreiter M, Schuppler J, Stockinger L. Cell proliferation and differentiation in the tracheal epithelium of the rat. Exp Cell Res 1968;50(2):377–382.Google Scholar
  62. 62.
    Evans MJ, Cabral-Anderson LJ, Freeman G. Role of the Clara cell in renewal of the bronchiolar epithelium. Lab Invest 1978;38(6):648–653.PubMedGoogle Scholar
  63. 63.
    Evans MJ, Cabral LJ, Stephens RJ, Freeman G. Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2. Exp Mol Pathol 1975;22(1):142–150.PubMedGoogle Scholar
  64. 64.
    Perl AK, Wert SE, Loudy DE, et al. Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli. Am J Respir Cell Mol Biol 2005;33(5):455–462.PubMedGoogle Scholar
  65. 65.
    Hong Ku, Reynolds SD, Watkins S, et al. Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol 2004;164(2):577–588.PubMedGoogle Scholar
  66. 66.
    Neuringer IP, Randell SH. Stem cells and repair of lung injuries. Respir Res 2004;5(1):6.PubMedGoogle Scholar
  67. 67.
    Borthwick DW, Shahbazian M, Krantz QT, et al. Evidence for stem-cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol 2001;24(6):662–670.PubMedGoogle Scholar
  68. 68.
    Voynow JA, Fischer BM, Roberts BC, Proia AD. Basallike cells constitute the proliferating cell population in cystic fibrosis airways. Am J Respir Crit Care Med 2005;172(8):1013–1018.PubMedGoogle Scholar
  69. 69.
    Boers JE, Ambergen AW, Thunnissen FB. Number and proliferation of Clara cells in normal human airway epithelium. Am J Respir Crit Care Med 1999;159(5 Pt 1):1585–1591.PubMedGoogle Scholar
  70. 70.
    Danto SI, Shannon JM, Borok Z, et al. Reversible transdifferentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol 1995;12(5):497–502.PubMedGoogle Scholar
  71. 71.
    Reddy R, Buckley S, Doerken M, et al. Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells. Am J Physiol Lung Cell Mol Physiol 2004;286(4):L658–L667.PubMedGoogle Scholar
  72. 72.
    Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121(6):823–835.PubMedGoogle Scholar
  73. 73.
    Demayo F, Minoo P, Plopper CG, et al. Mesenchymal-epithelial interactions in lung development and repair: are modeling and remodeling the same process? Am J Physiol Lung Cell Mol Physiol 2002;283(3):L510–L517.PubMedGoogle Scholar
  74. 74.
    Shannon JM, Hyatt BA. Epithelial-mesenchymal interactions in the developing lung. Annu Rev Physiol 2004;66:625–645.PubMedGoogle Scholar
  75. 75.
    Cardoso WV, Williams MC, Mitsialis SA, et al. Retinoic acid induces changes in the pattern of airway branching and alters epithelial cell differentiation in the developing lung in vitro. Am J Respir Cell Mol Biol 1995;12(5):464–476.PubMedGoogle Scholar
  76. 76.
    Lechner JF, Haugen A, Autrup H, et al. Clonal growth of epithelial cells from normal adult human bronchus. Cancer Res 1981;41(6):2294–2304.PubMedGoogle Scholar
  77. 77.
    Reynolds SD, Hong KU, Giangreco A, et al. Conditional Clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol 2000;278(6):L1256–L1263.PubMedGoogle Scholar
  78. 78.
    Kalinichenko VV, Lim L, Shin B, Costa RH. Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury. Am J Physiol Lung Cell Mol Physiol 2001;280(4):L695–L704.PubMedGoogle Scholar
  79. 79.
    Casalino-Matsuda SM, Monzon ME, Forteza RM. Epidermal growth factor receptor activation by epidermal growth factor mediates oxidant-induced goblet cell metaplasia in human airway epithelium. Am J Respir Cell Mol Biol 2006;34(5):581–591.PubMedGoogle Scholar
  80. 80.
    Li C, Xiao J, Hormi K, et al. Wnt5a participates in distal lung morphogenesis. Dev Biol 2002;248(1):68–81.PubMedGoogle Scholar
  81. 81.
    Motoyama J, Liu J, Mo R, et al. Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet 1998;20(1):54–57.PubMedGoogle Scholar
  82. 82.
    Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422(6929):313–337.PubMedGoogle Scholar
  83. 83.
    Weaver M, Yingling JM, Dunn NR, et al. BMP signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development 1999;126(18):4005–4015.PubMedGoogle Scholar
  84. 84.
    Muraoka RS, Bushdid PB, Brantley DM, et al. Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung. Dev Biol 2000;225(2):322–338.PubMedGoogle Scholar
  85. 85.
    Costa RH, Kalinichenko VV, Lim L. Transcription factors in mouse lung development and function. Am J Physiol Lung Cell Mol Physiol 2001;280(5):L823–L838.PubMedGoogle Scholar
  86. 86.
    Minoo P, Su G, Drum H, et al. Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(−/−) mouse embryos. Dev Biol 1999;209(1):60–71.PubMedGoogle Scholar
  87. 87.
    Pepicelli CV, Lewis PM, McMahon AP. Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol 1998;8(19):1083–1086.PubMedGoogle Scholar
  88. 88.
    Brody SL, Yan XH, Wuerffel MK, et al. Ciliogenesis and left-right axis defects in forkhead factor Hfh-4-null mice. Am J Respir Cell Mol Biol 2000;23(1):45–51.PubMedGoogle Scholar
  89. 89.
    Yang H, Lu MM, Zhang L, et al. GATA6 regulates differentiation of distal lung epithelium. Development 2002;129(9):2233–2246.PubMedGoogle Scholar
  90. 90.
    Fischer BM, Voynow JA. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. Am J Respir Cell Mol Biol 2002;26(4):447–452.PubMedGoogle Scholar
  91. 91.
    Longphre M, Li D, Gallup M, et al. Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells. J Clin Invest 1999;104(10):1375–1382.PubMedGoogle Scholar
  92. 92.
    Tyner JW, Kim EY, Ide K, et al. Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. J Clin Invest 2006;116(2):309–321.PubMedGoogle Scholar
  93. 93.
    Walter MJ, Morton JD, Kajiwara N, et al. viral induction of a chronic asthma phenotype and genetic segregation from the acute response. J Clin Invest 2002;110(2):165–175.PubMedGoogle Scholar
  94. 94.
    Tesfaigzi Y. Roles of apoptosis in airway epithelia. Am J Respir Cell Mol Biol 2006;34(5):537–547.PubMedGoogle Scholar
  95. 95.
    Bardales RH, Xie SS, Schaefer RF, Hsu SM. Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury. Am J Pathol 1996;149(3):845–852.PubMedGoogle Scholar
  96. 96.
    Fehrenbach H, Kasper M, Koslowski R, et al. Alveolar epithelial type II cell apoptosis in vivo during resolution of keratinocyte growth factor-induced hyperplasia in the rat. Histochem Cell Biol 2000;114(1):49–61.PubMedGoogle Scholar
  97. 97.
    Vermeer PD, Einwalter LA, Moninger TO, et al. Segregation of receptor and ligand regulates activation of epithelial growth factor receptor. Nature 2003;422(6929):322–326.PubMedGoogle Scholar
  98. 98.
    Madtes DK, Busby HK, Strandjord TP, Clark JG. Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycininduced lung injury in rats. Am J Respir Cell Mol Biol 1994;11(5):540–551.PubMedGoogle Scholar
  99. 99.
    Amishima M, Munakata M, Nasuhara Y, et al. Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway. Am J Respir Crit Care Med 1998;157(6 Pt 1):1907–1912.PubMedGoogle Scholar
  100. 100.
    Bandyopadhyay B, Fan J, Guan S, et al. A “traffic control” role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing. J Cell Biol 2006;172(7):1093–1105.PubMedGoogle Scholar
  101. 101.
    Morris DG, Huang X, Kaminski N, et al. Loss of integrin alpha(V)beta6-mediated TGF-beta activation causes MMP12-dependent emphysema. Nature 2003;422(6928):169–173.PubMedGoogle Scholar
  102. 102.
    Kumar AS, Gonzales LW, Ballard PL. Transforming growth factor-beta(1) regulation of surfactant protein B gene expression is mediated by protein kinase-dependent intracellular translocation of thyroid transcription factor-1 and hepatocyte nuclear factor 3. Biochim Biophys Acta 2000;1492(1):45–55.PubMedGoogle Scholar
  103. 103.
    Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 2005;166(5):1321–1332.PubMedGoogle Scholar
  104. 104.
    Fehrenbach H, Fehrenbach A, Pan T, et al. Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo. Eur Respir J 2002;20(5):1185–1197.PubMedGoogle Scholar
  105. 105.
    Yano T, Mason RJ, Pan T, et al. KGF regulates pulmonary epithelial proliferation and surfactant protein gene expression in adult rat lung. Am J Physiol Lung Cell Mol Physiol 2000;279(6):L1146–L1158.PubMedGoogle Scholar
  106. 106.
    Chedid M, Rubin JS, Csaky KG, Aaronson SA. Regulation of keratinocyte growth factor gene expression by interleukin 1. J Biol Chem 1994;269(14):10753–10757.PubMedGoogle Scholar
  107. 107.
    Waters CM, Savla U. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. J Cell Physiol 1999;181(3):424–432.PubMedGoogle Scholar
  108. 108.
    Putnins EE, Firth JD, Uitto VJ. Keratinocyte growth factor stimulation of gelatinase (matrix metalloproteinase-9) and plasminogen activator in histiotypic epithelial cell culture. J Invest Dermatol 1995;104(6):989–994.PubMedGoogle Scholar
  109. 109.
    Chelly N, Henrion A, Pinteur C, et al. Role of keratinocyte growth factor in the control of surfactant synthesis by fetal lung mesenchyme. Endocrinology 2001;142(5):1814–1819.PubMedGoogle Scholar
  110. 110.
    Miyazawa K, Shimomura T, Naka D, Kitamura N. Proteolytic activation of hepatocyte growth factor in response to tissue injury. J Biol Chem 1994;269(12):8966–8970.PubMedGoogle Scholar
  111. 111.
    Sakai T, Satoh K, Matsushima K, et al. Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization. Am J Respir Cell Mol Biol 1997;16(4):388–397.PubMedGoogle Scholar
  112. 112.
    Bryson Dg, McNulty MS, McCracken RM, Cush PF. Ultrastructural features of experimental parainfluenza type 3 virus pneumonia in calves. J Comp Pathol 1983;93(3):397–414.PubMedGoogle Scholar
  113. 113.
    Castleman WL, Chandler SK, Slauson DO. Experimental bovine respiratory syncytial virus infection in conventional calves: ultrastructural respiratory lesions. Am J Vet Res 1985;46(3):554–560.PubMedGoogle Scholar
  114. 114.
    Ibricevic A, Pekosz A, Walter MJ, et al. Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells. J Virol 2006;80(15):7469–7480.PubMedGoogle Scholar
  115. 115.
    Aherne W, Bird T, Court SD, et al. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol 1970;23(1):7–18.PubMedGoogle Scholar
  116. 116.
    Park JW, Taube C, Yang ES, et al. Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen. J Allergy Clin Immunol 2003;112(6):1078–1087.PubMedGoogle Scholar
  117. 117.
    Hashimoto K, Graham BS, Ho SB, et al. Respiratory syncytial virus in allergic lung inflammation increases MUC5AC and GOB-5. Am J Respir Crit Care Med 2004;170(3):306–312.PubMedGoogle Scholar
  118. 118.
    Schnapp LM, Donohoe S, Chen J, et al. Mining the acute respiratory distress syndrome proteome: identification of the insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung injury. Am J Pathol 2006;169(1):86–95.PubMedGoogle Scholar
  119. 119.
    Kaminski N, Allard JD, Pittet JF, et al. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci USA 2000;97(4):1778–1783.PubMedGoogle Scholar
  120. 120.
    Pittet JF, Griffiths MJ, Geiser T, et al. TGF-beta is a critical mediator of acute lung injury. J Clin Invest 2001;107(12):1537–1544.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Steven L. Brody
    • 1
  • Jeffrey J. Atkinson
    • 2
  1. 1.Division of Pulmonary and Critical Care Medicine, Department of Internal MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Internal Medicine/Pulmonary and Critical CareWashington University School of MedicineSt. LouisUSA

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