Pediatric Nephrology

, Volume 9, Issue 1, pp 104–111 | Cite as

Balance between matrix synthesis and degradation: a determinant of glomerulosclerosis

  • H. William Schnaper
Invited Review


In glomerular health and disease, the balance between extracellular matrix (ECM) protein synthesis and degradation determines the amount of matrix that accumulates locally. While cell and whole animal regulation of ECM synthesis has been the subject of ongoing study, attention has become focused on proteases that degrade matrix components only recently. Two major ECM protease systems have been defined. The plasminogen activators (PAs) are serine proteases that have matrix-degrading capability and also activate plasminogen to plasmin. Plasmin not only degrades ECM proteins, but also may activate members of the matrix metalloproteinase (MMP) family which comprise the second major matrix-degrading system. Specific biological antagonists of both the PAs and the MMPs tightly regulate proteolysis by these enzymes. All of these enzymes and inhibitors have been detected in the kidney, and their expression may be altered to facilitate ECM accumulation in conditions associated with matrix expansion, such as glomerulosclerosis. Work is in progress to determine how these systems are regulated in the kidney and to further define their contribution to the sclerotic process.

Key words

Glomerulosclerosis Proteases Metalloproteinases Plasminogen activators 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Thoenes W, Rumpelt JH (1977) The obsolescent renal glomerulus — collapse, sclerosis, hyalinosis, fibrosis. Virchows Arch [A] 377: 1–15Google Scholar
  2. 2.
    Striker LM-M, Killen PD, Chi E, Striker GE (1984) The composition of glomerulosclerosis. I. Studies in focal sclerosis, crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Lab Invest 51: 181–192PubMedGoogle Scholar
  3. 3.
    Warshaw BL, Edelbrock HH, Ettinger RB, Malekzadeh MH, Pennisi AJ, Uittenbogaart CH, Fine RN (1982) Progression to endstage renal disease in children with obstructive uropathy. J Pediatr 100: 183–187PubMedGoogle Scholar
  4. 4.
    Abrass CK, Peterson CV, Raugi GJ (1988) Phenotypic expression of collagen types in mesangial matrix of diabetic and nondiabetic rats. Diabetes 37: 1695–1702PubMedGoogle Scholar
  5. 5.
    Schnaper HW, Robson AM (1992) Nephrotic syndrome: minimal change disease, focal glomerulosclerosis, and related disorders. In: Schrier CW, Gottschalk CW (eds) Diseases of the kidney, 5th edn. Little Brown, Boston, pp 1731–1784Google Scholar
  6. 6.
    Diamond JR, Karnovsky MJ (1988) Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int 33: 917–924PubMedGoogle Scholar
  7. 7.
    Brenner BM (1985) Nephron adaptation to renal injury or ablation. Am J Physiol 249: F324-F337PubMedGoogle Scholar
  8. 8.
    Yamamoto T, Noble N, Miller DE, Border WA (1994) Sustained expression of TGF-β1 underlies development of progressive kidney fibrosis. Kidney Int 45: 916–927PubMedGoogle Scholar
  9. 9.
    Keane WF, Kasiske BL, O'Donnell MP (1988) Lipids and progressive glomerulosclerosis: a model analogous to atherosclerosis. Am J Nephrol 8: 261–271PubMedGoogle Scholar
  10. 10.
    Bruggeman LA, Horigan EA, Horikoshi S, Ray PE, Klotman PE (1991) Thromboxane stimulates synthesis of extracellular matrix proteins in vitro. Am J Physiol 261: F488-F494PubMedGoogle Scholar
  11. 11.
    Oomura A, Nakamura T, Arakawa M, Ooshima A, Isemura I (1989) Alterations in the extracellular matrix components in human glomerular disease. Virchows Arch [A] 415: 151–159Google Scholar
  12. 12.
    Unanue ER, Dixon FJ (1967) Experimental glomerulonephritis: immunological events and pathogenetic mechanisms. Adv Immunol 6: 1–90PubMedGoogle Scholar
  13. 13.
    Adler S, Striker LJ, Striker GE, Perkinson DT, Hobbert J, Couser WG (1986) Studies of progressive glomerular sclerosis in the rat. Am J Physiol 123: 553–562Google Scholar
  14. 14.
    Brazy PC, Kopp JB, Klotman PE (1991) Glomerulosclerosis and progressive renal disease. In: Keane WF (ed) Lipids and renal disease. Churchill-Livingstone, New York, pp 11–35Google Scholar
  15. 15.
    Latta H, Johnston WH, Stanley TM (1975) Sialoglycoproteins and filtration barriers in the glomerular capillary wall. J Ultrastruct Res 51: 354–376PubMedGoogle Scholar
  16. 16.
    Timpl R (1986) Recent advances in the biochemistry of glomerular basement membrane. Kidney Int 30: 293–298PubMedGoogle Scholar
  17. 17.
    Mounier F, Foidart J-M, Gubler M-C (1986) Distribution of extracellular matrix glycoproteins during normal development of human kidney. Lab Invest 54: 394–401PubMedGoogle Scholar
  18. 18.
    Schnaper HW, Kleinman HK (1993) Regulation of cell function by extracellular matrix. Pediatr Nephrol 7: 96–104PubMedGoogle Scholar
  19. 19.
    Foidart J-M, Foidart JB, Mahieu PR (1980) Synthesis of collagen and fibronectin by glomerular cells in culture. Renal Physiol 3: 183–192PubMedGoogle Scholar
  20. 20.
    Nakamura T, Ebihara I, Fukui M, Tomino Y, Koide H (1991) Effects of methylprednisoline on glomerular and medullary mRNA levels for extracellular matrices in puromycin aminonucleoside nephrosis. Kidney Int 40: 874–881PubMedGoogle Scholar
  21. 21.
    Kim Y, Kleppel MM, Butkowksi R, Mauer SM, Weislander J, Michael AF (1991) Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol 138: 413–420PubMedGoogle Scholar
  22. 22.
    Ledbetter SE, Copeland EJ, Noonan D, Vogelli G, Hassell JR (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 39: 196–203PubMedGoogle Scholar
  23. 23.
    Poulsom R, Kurkinen M, Prockop D, Boot-Handford RP (1988) Increased steady-state levels of laminin B1 mRNA in kidneys of long-term streptozotocin-diabetic rats. J Biol Chem 263: 10072–10076PubMedGoogle Scholar
  24. 24.
    Herrera-Acosta J (1994) The role of systemic and glomerular hypertension in progressive glomerular injury. Kidney Int 45 [Suppl 45]: S6-S10Google Scholar
  25. 25.
    Fogo A, Hawkins EP, Berry PL, Glick AD, McDonnell RC, Chiang ML, Ichikawa I (1990) Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int 38: 115–123PubMedGoogle Scholar
  26. 26.
    Myers BD (1991) Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset. J Clin Invest 88: 524–530PubMedGoogle Scholar
  27. 27.
    Robson AM, Mor J, Root ER, Jager BV, Shankel SW, Ingeler JR, Kienstra RA, Bricker NS (1979) Mechanism of proteinuria in nonglomerular renal disease. Kidney Int 16: 416–429PubMedGoogle Scholar
  28. 28.
    Bolton WK, Westervelt FB, Sturgill BC (1978) Nephrotic syndrome and focal glomerular sclerosis in aging man. Nephron 20: 307–315PubMedGoogle Scholar
  29. 29.
    Nath KA, Fischereder M, Hostetter TH (1994) The role of oxidants in progressive renal dijury. Kidney Int 45 [Suppl 45]: S111-S115Google Scholar
  30. 30.
    Purkerson ML, Joist JH, Yates J, Valdes A, Morrison A, Klahr S (1985) Inhibition of thromboxane sythesis ameliorates the progressive kidney disease of rats with subtotal renal ablation. Proc Natl Acad Sci USA 82: 193–197PubMedGoogle Scholar
  31. 31.
    Lovett DH, Martin M, Bursten S, Szamel M, Gemsa D, Resch K (1988) Interleukin 1 and the glomerular mesangium. III. IL-1-dependent stimulation of mesangial cell protein kinase activity. Kidney Int 34: 26–35PubMedGoogle Scholar
  32. 32.
    Iida H, Seifert R, Alpers CE, Gronwald RGK, Phillips PE, Pritzl P, Gordon K, Gown AM, Ross R, Bowen-Pope DF, Johnson RJ (1991) Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat. Proc Natl Acad Sci USA 88: 6560–6564PubMedGoogle Scholar
  33. 33.
    Ruef C, Budde K, Northemann W, Baumann M, Sterzel RB (1990) Interleukin 6 is an autocrine growth factor for mesangial cells. Kidney Int 38: 249–257PubMedGoogle Scholar
  34. 34.
    Fogo A, Ichikawa I (1989) Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol 9: 329–342PubMedGoogle Scholar
  35. 35.
    Hasegawa G, Nakano K, Sawada M, Uno K, Shibayama Y, Ienaga K, Kondo M (1991) Possible role of tumor necrosis factor and interleukin-1 in diabetic nephropathy. Kidney Int 40: 1007–1012PubMedGoogle Scholar
  36. 36.
    Oemar BS, Foellmer HG, Hodgdon-Anandant L, Rosenzweig SA (1991) Regulation of insulin-like growth factor receptors in diabetic mesangial cells. J Biol Chem 266: 2369–2372PubMedGoogle Scholar
  37. 37.
    Doi T, Striker LJ, Quaife C, Conti FG, Palmiter R, Behringer R, Brinster R, Striker GE (1988) Progressive glomerulosclerosis develops in transgenic mice expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1. Am J Pathol 131: 398–403PubMedGoogle Scholar
  38. 38.
    Doi T, Striker LJ, Kimata K, Peten EP, Yamada Y, Striker GE (1991) Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels. J Exp Med 173: 1287–1290PubMedGoogle Scholar
  39. 39.
    Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S, Miyazaki J-I, Hirano T, Kishimoto T (1989) IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 86: 7547–7551PubMedGoogle Scholar
  40. 40.
    Broekelmann TJ, Limper AH, Colby TV, McDonald JA (1991) Transforming growth factor β1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci USA 88: 6642–6646PubMedGoogle Scholar
  41. 41.
    Okuda S, Languino LR, Ruoslahti E, Border WA (1990) Elevated expression of transforming growth factor-β and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of extracellular matrix. J Clin Invest 86: 453–462PubMedGoogle Scholar
  42. 42.
    Kagami S, Border W, Ruoslahti E, Noble NA (1993) Coordinated espression of β1 integrins and transforming growth factor-β-induced matrix proteins in glomerulonephritis. Lab Invest 69: 68–76PubMedGoogle Scholar
  43. 43.
    Kreft B, Yokoyama H, Singer GG, Kelly VR (1983) Increased expression of distinct transforming growth factor β isoforms in lupus nephritis. J Am Soc Nephrol 4: 612Google Scholar
  44. 44.
    Yoshioka K, Takemura K, Murakami K, Okada M, Hino S, Miyamoto H, Maki S (1993) Transforming growth factor-β protein and mRNA in glomeruli in normal and diseased human kidneys. Lab Invest 68: 154–163PubMedGoogle Scholar
  45. 45.
    Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA (1993) Expression of transforming growth factor β is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci USA 90: 1814–1818PubMedGoogle Scholar
  46. 46.
    Yoshioka K, Takemura T, Tohda M, Akano N, Miyamoto H, Ooshima A, Maki S (1989) Glomerular localization of type III collagen in human kidney disease. Kidney Int 35: 1203–1211PubMedGoogle Scholar
  47. 47.
    Lubec G, Pollak A (1980) Reduced susceptibility of nonmatically glucosylated glomerular basement membrane to proteases. Renal Physiol 3: 4–8PubMedGoogle Scholar
  48. 48.
    Couchman JR, Beavan LA, McCarthy KJ (1994) Glomerular matrix: synthesis, turnover and role in mesangial expansion. Kidney Int 45: 328–335PubMedGoogle Scholar
  49. 49.
    Davies M, Martin J, Thomas GT, Lovett DH (1992) Proteinases and glomerular matrix turnover. Kidney Int 41: 671–678PubMedGoogle Scholar
  50. 50.
    Liotta LA, Goldfarb RH, Terranova VP (1981) Cleavage of laminin by thrombin and plasmin: alpha thrombin selectively cleaves the beta chain of laminin. Thromb Res 21: 663–673PubMedGoogle Scholar
  51. 51.
    Collen D (1980) On the regulation and control of fibrinolysis. Thromb Haemost 80: 77–89Google Scholar
  52. 52.
    Barnathan ES (1992) Characterization and regulation of the urose receptor of human endothelial cells. Fibrinolysis 6 [Suppl 1]: 1–9Google Scholar
  53. 53.
    Niedbala MJ, Stein-Picarella M (1993) Protein kinase C in tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator. Blood 81: 2608–2617PubMedGoogle Scholar
  54. 54.
    Schnaper HW, Mazar A, Barnathan ES, Kleinman HK (1994) Urokinase-type plasminogen activator (uPA) enhances endothelial cell differentiation through a non-proteolytic mechanism involving uPA receptor (uPAR) biding (abstract). Pediatr Res 35: 373AGoogle Scholar
  55. 55.
    Waltz DA, Sailor LZ, Chapman HA (1993) Cytokines induce urokinase-dependent adhesion of human myeloid cells. A regulatory role for plasminogen activator inhibitors. J Clin Invest 1541–1552Google Scholar
  56. 56.
    Woessner JF (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5: 2145–2154PubMedGoogle Scholar
  57. 57.
    Birkedal-Hansen H (1993) Role of matrix metalloproteinases in human periodontal disease. J Periodontol 64: 474–484PubMedGoogle Scholar
  58. 58.
    Liotta LA, Steeg PA, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336CrossRefPubMedGoogle Scholar
  59. 59.
    Rawlings ND, Barrett AJ (1993) Evolutionary families of peptidases. Biochem J 290: 205–218PubMedGoogle Scholar
  60. 60.
    Llorens-Cortes C, Huang H, Vicart P, Jasc J-M, Paulin D, Corvol P (1992) Identification and characterization of neutral endopeptidase in endothelial cells from venous or arterial origins. J Biol Chem 267: 14012–14018PubMedGoogle Scholar
  61. 61.
    Brown PD, Kleiner DE, Unsworth EJ, Stetler-Stevenson WG (1993) Cellular activation of the 72 kDa type IV procollagenase/TIMP-2 complex. Kidney Int 43: 163–170PubMedGoogle Scholar
  62. 62.
    Chen W-T (1992) Membrane proteases: roles in tissue remodeling and tumour invasion. Curr Opin Cell Biol 4: 802–809PubMedGoogle Scholar
  63. 63.
    Carmichael DF, Sommer A, Thompson RC, Anderson DC, Smith CG, Welgus HG, Stricklin GP (1986) Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc Natl Acad Sci USA 83: 2407–2411PubMedGoogle Scholar
  64. 64.
    DeClerck YA, Yean T-D, Ratzkin BJ, Lu HS, Langley KE (1989) Purification and characterization of two related but distinct metalloproteinase inhibitors secreted by bovine aortic endothelial cells. J Biol Chem 264: 17445–17453PubMedGoogle Scholar
  65. 65.
    Stetler-Stevenson WG, Krutzsch HC, Liotta LA (1989) Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J Biol Chem 264: 17374–17378PubMedGoogle Scholar
  66. 66.
    Leco KJ, Khohka R, Pavloff N, Hawkes SP, Edwards DR (1994) Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. J Biol Chem 269: 9352–9360PubMedGoogle Scholar
  67. 67.
    Goldberg GI, Marmer BL, Grant GA, Eisen AZ, Wilhelm S, He C (1989) Human 72-kilodalton type IV collagenase forms a complex with tissue inhibitor of metalloproteinases designated TIMP-2. Proc Natl Acad Sci USA 86: 8207–8211PubMedGoogle Scholar
  68. 68.
    Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T (1992) Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202: 471–476PubMedGoogle Scholar
  69. 69.
    Crabbe T, Smith B, O'Connel J, Docherty A (1994) Human progelatinase A can be activates by matrilysin. FEBS Lett 345: 14–16PubMedGoogle Scholar
  70. 70.
    Ogata Y, Enghild JJ, Nagase H (1992) Matrix metalloproteinase 3 (stromelysin) activates the precursor for human matrix metalloproteinase 9. J Biol Chem 267: 3581–3584PubMedGoogle Scholar
  71. 71.
    Baricos WH, Cortez SL, El-Dahr SS, Schnaper HW (1995) ECM degradation by cultured human mesangial cells is mediated by a plasminogen activator/plasmin/matrix metalloproteinase 2 cascade. Kidney Int (in press)Google Scholar
  72. 72.
    Desrochers PE, Jeffrey JJ, Weiss SJ (1991) Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity. J Clin Invest 87: 2258–2265PubMedGoogle Scholar
  73. 73.
    Marcotte PA, Kozan IM, Dorwin SA, Ryan JM (1992) The matrix metalloproteiase PUMP-1 catalyzes formation of low molecular weight (pro)urokinase in cultures of normal human kidney cells. J Biol Chem 267: 13803–13806PubMedGoogle Scholar
  74. 74.
    Brenner CA, Adler RR, Rappolee DA, Pedersen RA, Werb Z (1989) Genes for extracellular matrix-degrading metalloprotees and their inhibitor, TIMP, are expressed during early mammalian development. Genes Dev 3: 848–859PubMedGoogle Scholar
  75. 75.
    Hecht PM, Anderson KV (1992) Extracellular proteases and embryonic pattern formation. Trends Cell Biol 2: 197–202PubMedGoogle Scholar
  76. 76.
    Girard MT, Matsubara M, Kublin C, Tessier MJ, Cintron C, Fini ME (1993) Stromal fibroblasts synthesize collagenase and stromelysin during long-term tissue remodeling. J Cell Sci 104: 1001–1011PubMedGoogle Scholar
  77. 77.
    Stricklin GP, Bauer EA, Jeffrey JJ, Eisen AZ (1977) Human skin collagenase: isolation of precursor and active forms from both fibroblasts and organ cultures. Biochemistry 16: 1607–1615PubMedGoogle Scholar
  78. 78.
    Welgus HG, Campbell EJ, Cury JD, Eisen AZ, Senior RM, Wilhelm SM, Goldberg GI (1990) Neutral metalloproteinases produced by human monoculear phagocytes. Enzyme profile, regulation and expression during cellular development. J Clin Invest 86: 1496–1502PubMedGoogle Scholar
  79. 79.
    Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI (1989) SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 264: 17213–17221PubMedGoogle Scholar
  80. 80.
    Carome MA, Striker LJ, Peten EP, Moore J, Yang C-H, Stetler-Stevenson WG, Striker GE (1993) Human glomeruli express TIMP-1 mRNA and TIMP-2 protein and mRNA. Am J Physiol 264: F923-F929PubMedGoogle Scholar
  81. 81.
    Le Q, Cortez S, Nguyen H, Shah S, Baricos W (1992) Glomerular neutral metalloproteinase: characterization and activity in animal models of human glomerular disease. Matrix [Suppl] 1: 415–416PubMedGoogle Scholar
  82. 82.
    Wong AP, Cortez SL, Baricos WH (1992) Role of plasmin and gelatinase in extracellular matrix degradation by cultured rat mesangial cells. Am J Physiol 263: 1112–1118Google Scholar
  83. 83.
    Aya N, Yoshioka K, Murakami K, Hino S, Okada K, Matsuo O, Maki S (1992) Tissue-type plasminogen activator and its inhibitor in human glomerulonephritis. J Pathol 166: 289–295PubMedGoogle Scholar
  84. 84.
    Tomooka S, Border WA, Marshall BC, Noble NA (1992) Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. Kidney Int 42: 1462–1469PubMedGoogle Scholar
  85. 85.
    Marti HP, Lee L, Kashgarian M, Lovett DH (1994) Transforming growth factor-β1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase. Am J Pathol 144: 82–94PubMedGoogle Scholar
  86. 86.
    Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA (1991) Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int 40: 1020–1031PubMedGoogle Scholar
  87. 87.
    Paczek L, Teschner M, Schaefer RM, Kovar J, Romen W, Heidland A (1992) Intraglomerular proteinase activity in adriamycin-induced nephropathy. Nephron 60: 81–86PubMedGoogle Scholar
  88. 88.
    Teschner M, Schaefer RM, Paczek L, Heidland A (1992) Effect of renal diseases on glomerular proteinases. Miner Electrolyte Metab 18: 92–96PubMedGoogle Scholar
  89. 89.
    Reckelhoff JF, Tygart VL, Mitias MM, Walcott JL (1993) STZ-induced diabetes results in decreased activity of glomerular cathepsin and metalloprotease in rats. Diabetes 42: 1425–1432PubMedGoogle Scholar
  90. 90.
    Fukui M, Nakamura T, Ebihara I, Osada S, Tomino Y, Koide H (1992) Diet protein restriction reduces increased mRNA levels encoding for extracellular matrix (ECM) components, metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in glomeruli from focal glomerulosclerosis (FGS) (abstract). J Am Soc Nephrol 3: 630Google Scholar
  91. 91.
    Reckelhoff JF, Bayliss C (1993) Glomerular metalloprotease activity in the aging rat kidney: inverse correlation with injury. J Am Soc Nephrol 3: 1835–1838PubMedGoogle Scholar
  92. 92.
    Nakamura T, Fukui M, Ebihara I, Tomino Y, Koide H (1994) Low protein diet blunts the rise in glomerular gene expression in focal glomerulosclerosis. Kidney Int 45: 1593–1605PubMedGoogle Scholar
  93. 93.
    Alexander CM, Werb Z (1992) Targeted disruption of the tissue inhibitor of metalloproteinases gene increases the invasive behavior of primitive mesenchymal cells derived from embryonic stem cells in vitro. J Cell Biol 118: 727–739PubMedGoogle Scholar
  94. 94.
    Schnaper HW, Grant DS, Stetler-Stevenson WG, Fridman R, D'Orazi G, Bird RE, Hoyhtya M, Fuerst TR, Quigley J, French D, Kleinman HK (1993) Type IV collagenases and TIMPs modulate endothelial cell morphogenesis in vitro. J Cell Physiol 156: 235–246PubMedGoogle Scholar
  95. 95.
    Le Q, Shah S, Nguyen H, Cortez S, Baricos W (1991) A novel metalloproteinase present in freshly isolated rat glomeruli. Am J Physiol 260: F555-F561PubMedGoogle Scholar
  96. 96.
    Johnson R, Yamabe H, Chen YP, Campbell C, Gordon K, Baker P, Lovett D, Couser WG (1991) Glomerular epithelial cells secrete a glomerular basement membrane-degrading metalloproteinase. J Am Soc Nephrol 2: 1388–1397Google Scholar
  97. 97.
    Marti H-P, McNeil L, Davies M, Martin J, Lovett DH (1993) Homology cloning of rat 72 kDa type IV collagenase: cytokine and second messenger inducibility in glomerular mesangial cells. Biochem J 291: 441–446PubMedGoogle Scholar
  98. 98.
    Campbell EJ, Cury JD, Shapiro SD, Goldberg GI, Welgus HG (1991) Neutral proteinases of human mononuclear phagocytes. Cellular differentiation markedly alters cell phenotype for serineproteases, metalloproteinases and tissue inhibitor of metalloproteinases. J Immunol 146: 1286–1293PubMedGoogle Scholar
  99. 99.
    Overall CM, Wrana JL, Sodek J (1989) Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitors expression in human fibroblasts by transforming growth factor-β. J Biol Chem 264: 1860–1869PubMedGoogle Scholar
  100. 100.
    Alexander JP, Bradley JMB, Gaboure JD, Acott TS (1990) Expression of matrix metalloproteinases and inhibitor by human retinal pigment epithelium. Invest Ophthalmol Vis Sci 31: 2520–2528PubMedGoogle Scholar
  101. 101.
    Lefebvre V, Peeters-Joris C, Vaes G (1991) Production of gelatin-degrading matrix metalloproteinases (‘type IV collagnases’) and inhibitors by articular chondrocytes during their dedifferentiation by serial subcultures and under stimulation by interleukin-1 and tumor necrosis factor α. Biochim Biophys Acta 1094: 8–18PubMedGoogle Scholar
  102. 102.
    Fini ME, Girard MT (1990) The pattern of metalloproteinase expression by corneal fibroblasts is altered by passage in cell culture. J Cell Sci 97: 373–383PubMedGoogle Scholar
  103. 103.
    Schnaper HW, Kopp JB, Stetler-Stevenson WG, Bruggeman LA, Klotman PE, Kleinman HK (1993) Regulation of TIMP-2 splice variants is independent of TGF-β in cultured glomerular mesangial cells. J Am Soc Nephrol 3: 664Google Scholar
  104. 104.
    Blau HM (1992) Differentiation requires continuous active control. Annu Rev Biochem 61: 1213–1230PubMedGoogle Scholar
  105. 105.
    Striker GE, Lange MA, McKay K, Bernstein K, Striker LJ (1987) Glomerular cells in vitro. Adv Nephrol 16: 169–186Google Scholar

Copyright information

© IPNA 1995

Authors and Affiliations

  • H. William Schnaper
    • 1
  1. 1.Division of Nephrology, Department of PediatricsChildren's Memorial Hospital and Northwestern University Medical SchoolChicagoUSA

Personalised recommendations