Summary
We investigated the distribution of extracellular matrix components such as fibronectin, laminin, type III, IV, V, and VI collagens and heparan sulfate proteoglycan (HSPG) in normal and diseased glomeruli using the indirect immunofluorescence method. This study included 96 renal biopsies: 7 controls, 3 minimal change nephrotic syndrome (MCNS), 47 mesangial proliferative glomerulonephritis (PGN), 25 membranous nephropathy (MN) and 14 membranoproliferative glomerulonephritis (MPGN) including 3 lupus nephritis. Fibronectin was detected predominantly in the mesangium and less prominently in the glomerular basement membrane (GBM) of normal glomeruli. Laminin and type IV collagen were present in the mesangium and GBM, type III collagen in the interstitium, and type V collagen in the mesangium, interstitium and a part of GBM. Type VI collagen was observed in the mesangium, interstitium and slightly in GBM. Anti-HSPG antibody reacted with the mesangium and GBM. MCNS showed a distribution of these antigens similar to that in normal controls. The finding that staining for HSPG was not decreased in the GBM and mesangium indicated that there was no change in the core protein of HSPG. Fibronectin, laminin, type IV collagen and HSPG were increased in the thickened GBM of MN and in the expanded mesangium of PGN. In MPGN, these matrix components were increased in the mesangium and GBM with remarkable increase of type V and VI collagens. While type III collagen was not found in normal glomeruli, it became detectable in the mesangium and a part of GBM in MPGN. No significant decrease in the intensity of fluorescence for HSPG was observed in the glomeruli from nephrotic patients.
These findings suggest that proteinuria might be caused by the structural alteration in the glycosaminoglycan portion of HSPG, changes in any anionic material other than HSPG, or both, and also indicate that the glomerular mesangial sclerosis is closely related to the increase of type V and VI collagens.
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References
Becker J, Schuppan D, Hahn EG, Albert G, Reichart P (1986) The immunohistochemical distribution of collagens type IV, V, VI and of laminin in the human oral mucosa. Arch Oral Biol 31:179–186
Chung E, Rhodes RK, Miller EJ (1976) Isolation of three collagenous components of probable basement membrane origin from several tissues. Biochem Biophys Res Commun 71:1167–1174
Caulfield JP, Farquhar MG (1978) Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 39:505–512
Dixon AJ, Burns J, Dunnill MS, Mc Gee J (1980) Distribution of fibronectin in normal and dieseased human kidneys. J Clin Pathol 33:1021–1028
Foidart JB, Foidart JM, Hassell J, Mahieu P (1983) Localization by immunofluorescent microscopy of several collagen types and of a basement membrane proteoglycan in rat glomerular epithelial and mesangial cell cultures. Renal Physiol Basel 6:163–170
Frenk SA, Craig JM, Metcoff J (1955) Experimental nephrotic syndrome in rats by aminonucleoside. Proc Soc Exp Biol Med 89:424–427
Groggel GC, Hovingh P, Border WA, Linker A (1987) Changes in glomerular heparan sulfate in puromycin aminonucleoside nephrosis. Am J Pathol 128:521–527
Groggel GC, Stevenson J, Hovingh P, Linker A, Border WA (1988) Changes in heparan sulfate correlate with increased permeability. Kidney Int 33:517–523
Hall GH, Farson DA, Bissel MJ (1982) Lumen formation by epithelial cell lines in response to collagen overlay: a morphogenetic model in culture. Proc Natl Acad Sci USA 79:4672–4676
Hassell JR, Robey PG, Barrach HJ, Wilczek J, Rennard SI, Martin GR (1980) Isolation of a heparan sulfate - containing proteoglycan from basement membrane. Proc Natl Acad Sci USA 77:4494–4498
Hessle H, Engvall E (1984) Type VI collagen; Studies on its localization, structure, and biosynthetic form with monoclonal antibodies. J Biol Chem 259:3955–3961
Isemura M, Sato N, Yamaguchi Y, Aikawa J, Munakata H, Hayashi N, Yosizawa Z, Nakamura T, Kubota A, Arakawa M, Hsu C (1987) Isolation and characterization of fibronectin-binding proteoglycan carrying both heparan sulfate and dermatan sulfate chains from human placenta. J Biol Chem 262:8926–8933
Jander R, Rauterberg J, Voss B, von Bassewitz DB (1981) A cystein-rich collagenous protein from bovine placenta: Isolation of its constituent polypeptide chains and some properties of the non-denatured protein. Eur J Biochem 114:17–25
Kanwar YS, Linker A, Farquhar MG (1980) Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol 86:688–693
Kanwar YS, Jakubowski ML (1984) Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis. Kidney Int 250:613–618
Killen PD, Melcion C, Bonadio JF, Morel-Maroger L, Striker GE (1982) Glomerular response to immunologic injury, studies on progression. Springer Semin Immunopathol 5:297–320
Kleinman HK, Klebe RJ, Martin GR (1981) Role of collagenous matrices in the adhesion and growth of cells. J Cell Biol 88:473–485
Kreisberg JI, Karnovsky MJ (1983) Glomerular cells in culture. Kidney Int 23:439–447
Lelongt B, Makino H, Kanwar YS (1987) Status of glomerular proteoglycans in aminonucleoside nephrosis. Kidney Int 31:1299–1310
Lovett DH, Sterzel RB (1986) Cell culture approaches to the analysis of glomerular inflammation. Kidney Int 30:246–254
Martinenz-Hernandez A, Gay S, Miller EJ (1982) Ultrastructural localization of type V collagen in rat kidney. J Cell Biol 92:343–349
Martinez-Hernandez A, Amenta PS (1983) The basement membrane in pathology. Lab Invest 48:656–677
Nakamura T (1986) Monoclonal antibodies to human glomerular antigens: II. Using human adult kidney components as antigens. Clin Immunol Immunopathol 41:399–408
Nakamura T, Oite T, Kazama T, Suzuki S, Orikasa M, Arakawa M, Shimizu F (1988) Monoclonal antibodies to human glomerular antigens. Virchows Archiv [A] 412:573–582
Ooshima A, Muragaki Y, Bai Y, Matsumoto E, Miyamoto S, Iwata K (1985) Production of monoclonal antibodies to human type III, IV and VI collagens: An appreciation to immunohistochemistry in malignant neoplasms. In: Shibata S (ed) Basement Membranes. Elsevier, Amsterdam, pp 449–450
Pettersson EE, Colvin RB (1978) Cold-insoluble globulin (fibronectin, LETS protein) in normal an diseased human glomeruli: Papain-sensitive attachment to normal glomeruli and deposition in crescents. Clin Immunol Immunopathol 11:425–436
Roll FJ, Madri JA, Albert J, Furthmayr H (1980) Codistribution of collagen type IV and AB2 in basement membranes and mesangium of the kidney: an immunoferritin study of ultrathin frozen sections. J Cell Biol 85:597–616
Rosenzweig LJ, Kanwar YS (1982) Removal of sulfated (heparan sulfate) or nunsulfated (hyaluronic acid) glycosaminoglycans results in increased permeability of glomerular basement membrane to125I-bovine serum albumin. Lab Invest 47:177–184
Scheinman JI, Foidart JM, Michael AF (1980) The immunohistology of glomerular antigens. V. The collagenous antigens of the glomerulus. Lab Invest 43:373–381
Striker GE, Killen PD, Farin FM (1980) Human glomerular cells in vitro: Isolation and characterization. Transplant Proc 12:88–99
Striker LM, Killen PD, Chi E, Striker GE (1984) The composition of glomerulosclerosis. I. Studies in focal sclerosis, crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Lab Invest 51:181–192
Suzuki Y, Matsuki K, Oite T, Schimizu F, Koda Y, Arakawa M (1984) Localization of glomerular fibronectin in human and experimental glomerulonephritis. Jpn J Nephrol 26:263–273
Timpl R, Rhode H, Robey PG, Rennard SI, Foidart JM, Martin GR (1979) Laminin - A glycoprotein from basement membranes. J Biol Chem 254:9933–9937
Vernier RL, Papermaster BW, Good RA (1959) Aminonucleoside nephrosis. I. Electron microscopic study of the renal lesions in rats. J Exp Med 109:115–126
Von der Mark H, Aumailley M, Wick G, Fleischmajer R, Timpl R (1984) Immunochemistry, genuine size and tissue localization of collagen VI. Eur J Biochem 142:493–502
Weiss MA, Ooi BS, Ooi YM, Engvall E, Ruoslahti E (1979) Immunofluorescent localization of fibronectin in the human kidney. Lab Invest 41:340–347
Wicha MS, Lowrie G, Kohn E, Bagavandoss P, Mahn T (1982) Extracellular matrix promotes mammary epithelial growth and differentiation in vitro. Proc Natl Acad Sci USA 79:3213–3217
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Oomura, A., Nakamura, T., Arakawa, M. et al. Alterations in the extracellular matrix components in human glomerular diseases. Vichows Archiv A Pathol Anat 415, 151–159 (1989). https://doi.org/10.1007/BF00784353
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DOI: https://doi.org/10.1007/BF00784353