Summary
The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88±6 vs 48±4 ng/103 glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186±6 U/mg protein vs 286±14 U/mg protein, at pH 7.4: 152±12 U/mg protein vs 193±12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.
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Kasiske BL, Cleary MP, O'Donnel MP, Keane WF (1985) Effects of genetic obesity on renal structure and function in the Zucker rat. J Lab Clin Med 106: 598–604
Zucker LM (1965) Hereditary obesity in the rat associated with hyperlipidemia. Ann NY Acad Sci 131: 447–458
Klahr S, Schreiner G, Ichikawa I (1988) The progression of renal disease. N Eng J Med 318: 1657–1666
Teschner M, Paczek L, Schaefer RM, Heidland A (1991) Obese Zucker rat: potential role of intraglomerular proteolytic enzymes in the development of glomerulosclerosis. Res Exp Med (in press)
Spiro RG (1967) Studies on the renal glomerular basement membrane. Preparation and chemical composition. J Biol Chem 242: 1915–1919
Cooper TW, Bauer EA, Eisen AZ (1983) Enzyme-linked Immunosorbent Assay for human skin collagenase. Collagen Rel Res 3: 205–216
Haapatanta T, Gustafsoon JA, Glauman H (1983) Isolation of mitochondrial lysosomes and mitosomes from rat ventral prostate with a note on inverted microsomal vesicles. Arch Biochem Biophys 223: 458–467
Rennard SI, Berg R, Martin GR, Foidard JM, Robey PG (1980) Enzyme-linked Immunoassay (ELISA) for connective tissue components. Anal Biochem 104: 205–214
North MJ (1989) Prevention of unwanted proteolysis. In: Baynon RJ, Bond JS (eds), Proteolytic enzymes. Oxford University Press, London, pp 105–124
Lowry OH, Rosebrough NJ, Farr AC, Randall RJ (1951) Protein measurements with the Folin phenol reagent. J Biol Chem 193: 265–275
Ruoslahti E (1988) Fibronectin and its receptors. Ann Rev Biochem 57: 375–413
Hynes RO, Yamada KM (1982) Fibronectins: multifunctional modular glycoproteins. J Cell Biol 95: 369–377
Stathakis N, Fountas A, Tsianos E (1981) Plasma fibronectin in normal subjects and in various disease states. J Clin Pathol 34: 504–508
Labat-Robert J, Leutenegger M, Llopis G, Ricard Y, Berouette JC (1984) Plasma and tissue fibronectin in diabetes. Clin Physiol Biochem 2: 39–48
Gauss-Müller V, Kleinmann HK, Martin GF, Schiffmann E (1980) Role of attachment factors and attractants in fibroblasts chemotaxis. J Lab Clin Med 96: 1071–1080
Cosio FG, Sedmak DD, Nahman NS (1990) Cellular receptors for matrix proteins in normal human kidney and human mesangial cells. Kidney Int 38: 886–895
Border WA, Okuda S, Nakamura T (1989) Extracellular matrix and glomerular disease. Semin Nephrol 9: 307–317
Cohen MP, Saini R, Klepser H, Vasanthi VL (1987) Fibronectin binding to glomerular basement membrane is altered in diabetes. Diabetes 36: 758–763
Oberky TK, Mosher DF, Mills MD (1979) Localisation of fibronectin within the renal glomerulus and its production by cultured glomerular cells. Am J Pathol 96: 651–662
Musso R, Longo A, Cacciola RR, Lombardo A, Ginstrolisi R, Cacciola E (1989) Elevated fibronectin plasma levels in diabetes mellitus are expression of increased synthesis and release by vascular endothelium. Thromb Haemostasis 61: 150–151
Phou-Thonh L, Robert L, Berouette JC, Labat-Robert J (1987) Increased biosynthesis and processing of fibronectin in fibroblasts from diabetic mice. Proc Natl Acad Sci USA 84: 1911–1915
Hostetter TH (1986) Pathogenesis of diabetic nephropathy. In: Mitch WE, Brenner BM, Stein JH (eds) Progressive nature of renal disease. Churchill Livingstone New York, London, Melbourne, pp 149–166
O'Donnal MP, Kasiske BL, Cleary MP, Kean WF (1985) Effects of genetic obesity on renal structure and function in the Zucker rat. 2. Micropuncture studies. J Lab Clin Med 106: 605–610
Davies M, Martin J, Thomas GJ, Coles GA, Lovett DH (1987) Degradation of glomerular extracellular matrices; In: BM Price, Thudson LE, (eds) Renal basement membranes in health and disease, Academic Press, London, pp 181–201
Tarsio JF, Wigness B, Rhode TD, Rupp WM, Buchwald H, Furcht LT (1985) Nonenzymatic glycation of fibronectin and alterations in the molecular association of cell matrix and basement membrane components in diabetes mellitus. Diabetes 34: 477–484
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Paczek, L., Teschner, M., Schaefer, R.M. et al. Intraglomerular fibronectin accumulation and degradation in obese Zucker rats. Diabetologia 34, 786–789 (1991). https://doi.org/10.1007/BF00408351
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DOI: https://doi.org/10.1007/BF00408351