Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Oct;139(4):889–899.

Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions.

A Nerlich 1, E Schleicher 1
PMCID: PMC1886324  PMID: 1928305

Abstract

The immunohistochemical localization of the extracellular matrix was examined in 31 cases with different degrees of human diabetic nephropathy using antisera to human collagen types I, III, IV, V, fibronectin, laminin, and basement-membrane-associated heparan sulfate proteoglycan (HSPG). In normal glomeruli, HSPG was predominantly localized in the glomerular basement membrane and in the mesangium, and to minor extent in the basement membranes of tubules and Bowman's capsule. Collagen IV and laminin were distributed in glomerular basement membrane and mesangium in minor amounts. Interstitial collagens usually do not occur within glomeruli except for collagen V which has a light microscopic glomerular distribution similar to collagen IV. In diabetic diffuse glomerulosclerosis, the enlarged mesangial matrix showed an increased staining reaction for collagen IV, V, laminin, and fibronectin whereas the staining pattern of HSPG was markedly reduced. Early, small nodular lesions in diabetic glomeruli were similarly positive for most of the basement membrane components, whereas HSPG remained absent. With an increase in the diameter of the noduli, however, the staining reaction for all basement membrane components diminished, whereas interstitial collagens V and III, but not collagen I, were present in these noduli in substantial amounts. These initial studies provide evidence that the changes in the glomerular matrix in diabetic nephropathy may be divided into distinct and progressing stages of lesions. The reduced amount of HSPG even in slight, early lesions may represent the morphologic correlate to the impaired filter function of the glomerular basement membrane.

Full text

PDF
889

Images in this article

894Figure 3
on p.894
896Figure 5
on p.896
891Figure 1
on p.891
893Figure 2
on p.893
895Figure 4
on p.895

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahamson D. R. Recent studies on the structure and pathology of basement membranes. J Pathol. 1986 Aug;149(4):257–278. doi: 10.1002/path.1711490402. [DOI] [PubMed] [Google Scholar]
  2. Abrass C. K., Peterson C. V., Raugi G. J. Phenotypic expression of collagen types in mesangial matrix of diabetic and nondiabetic rats. Diabetes. 1988 Dec;37(12):1695–1702. doi: 10.2337/diab.37.12.1695. [DOI] [PubMed] [Google Scholar]
  3. Barsky S. H., Rao N. C., Restrepo C., Liotta L. A. Immunocytochemical enhancement of basement membrane antigens by pepsin: applications in diagnostic pathology. Am J Clin Pathol. 1984 Aug;82(2):191–194. doi: 10.1093/ajcp/82.2.191. [DOI] [PubMed] [Google Scholar]
  4. Bendayan M. Alteration in the distribution of type IV collagen in glomerular basal laminae in diabetic rats as revealed by immunocytochemistry and morphometrical approach. Diabetologia. 1985 Jun;28(6):373–378. doi: 10.1007/BF00283147. [DOI] [PubMed] [Google Scholar]
  5. Brown D. M., Klein D. J., Michael A. F., Oegema T. R. 35S-glycosaminoglycan and 35S-glycopeptide metabolism by diabetic glomeruli and aorta. Diabetes. 1982 May;31(5 Pt 1):418–425. doi: 10.2337/diab.31.5.418. [DOI] [PubMed] [Google Scholar]
  6. Brownlee M., Cerami A. The biochemistry of the complications of diabetes mellitus. Annu Rev Biochem. 1981;50:385–432. doi: 10.1146/annurev.bi.50.070181.002125. [DOI] [PubMed] [Google Scholar]
  7. Caulfield J. P., Farquhar M. G. Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest. 1978 Nov;39(5):505–512. [PubMed] [Google Scholar]
  8. Cohen M. P., Klepser H., Wu V. Y. Undersulfation of glomerular basement membrane heparan sulfate in experimental diabetes and lack of correction with aldose reductase inhibition. Diabetes. 1988 Oct;37(10):1324–1327. doi: 10.2337/diab.37.10.1324. [DOI] [PubMed] [Google Scholar]
  9. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  10. Falk R. J., Scheinman J. I., Mauer S. M., Michael A. F. Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes. 1983 May;32 (Suppl 2):34–39. doi: 10.2337/diab.32.2.s34. [DOI] [PubMed] [Google Scholar]
  11. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  12. Kanwar Y. S., Rosenzweig L. J., Linker A., Jakubowski M. L. Decreased de novo synthesis of glomerular proteoglycans in diabetes: biochemical and autoradiographic evidence. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2272–2275. doi: 10.1073/pnas.80.8.2272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klein D. J., Brown D. M., Oegema T. R. Glomerular proteoglycans in diabetes. Partial structural characterization and metabolism of de novo synthesized heparan-35SO4 and dermatan-35SO4 proteoglycans in streptozocin-induced diabetic rats. Diabetes. 1986 Oct;35(10):1130–1142. doi: 10.2337/diab.35.10.1130. [DOI] [PubMed] [Google Scholar]
  14. Kurkinen M., Vaheri A., Roberts P. J., Stenman S. Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest. 1980 Jul;43(1):47–51. [PubMed] [Google Scholar]
  15. Martinez-Hernandez A., Amenta P. S. The basement membrane in pathology. Lab Invest. 1983 Jun;48(6):656–677. [PubMed] [Google Scholar]
  16. Martinez-Hernandez A., Gay S., Miller E. J. Ultrastructural localization of type V collagen in rat kidney. J Cell Biol. 1982 Feb;92(2):343–349. doi: 10.1083/jcb.92.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mynderse L. A., Hassell J. R., Kleinman H. K., Martin G. R., Martinez-Hernandez A. Loss of heparan sulfate proteoglycan from glomerular basement membrane of nephrotic rats. Lab Invest. 1983 Mar;48(3):292–302. [PubMed] [Google Scholar]
  18. Olgemöller B., Schleicher E., Nerlich A., Wagner E. M., Gerbitz K. D. Isolation, characterization and immunological determination of basement membrane-associated heparan sulfate proteoglycan. Biol Chem Hoppe Seyler. 1989 Dec;370(12):1321–1329. doi: 10.1515/bchm3.1989.370.2.1321. [DOI] [PubMed] [Google Scholar]
  19. Parthasarathy N., Spiro R. G. Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes. 1982 Aug;31(8 Pt 1):738–741. doi: 10.2337/diab.31.8.738. [DOI] [PubMed] [Google Scholar]
  20. Paulsson M. Noncollagenous proteins of basement membranes. Coll Relat Res. 1987 Dec;7(6):443–461. doi: 10.1016/s0174-173x(87)80042-0. [DOI] [PubMed] [Google Scholar]
  21. Rohrbach D. H., Hassell J. R., Kleinman H. K., Martin G. R. Alterations in the basement membrane (heparan sulfate) proteoglycan in diabetic mice. Diabetes. 1982 Feb;31(2):185–188. doi: 10.2337/diab.31.2.185. [DOI] [PubMed] [Google Scholar]
  22. Rohrbach R. Reduced content and abnormal distribution of anionic sites (acid proteoglycans) in the diabetic glomerular basement membrane. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(2):127–135. doi: 10.1007/BF02899023. [DOI] [PubMed] [Google Scholar]
  23. Roll F. J., Madri J. A., Albert J., Furthmayr H. Codistribution of collagen types IV and AB2 in basement membranes and mesangium of the kidney. an immunoferritin study of ultrathin frozen sections. J Cell Biol. 1980 Jun;85(3):597–616. doi: 10.1083/jcb.85.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schleicher E. D., Wagner E. M., Olgemöller B., Nerlich A. G., Gerbitz K. D. Characterization and localization of basement membrane-associated heparan sulfate proteoglycan in human tissues. Lab Invest. 1989 Sep;61(3):323–332. [PubMed] [Google Scholar]
  25. Schleicher E., Wieland O. H. Changes of human glomerular basement membrane in diabetes mellitus. J Clin Chem Clin Biochem. 1984 Mar;22(3):223–227. doi: 10.1515/cclm.1984.22.3.223. [DOI] [PubMed] [Google Scholar]
  26. Shimomura H., Spiro R. G. Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes. Decreased levels of heparan sulfate proteoglycan and laminin. Diabetes. 1987 Mar;36(3):374–381. doi: 10.2337/diab.36.3.374. [DOI] [PubMed] [Google Scholar]
  27. Stow J. L., Sawada H., Farquhar M. G. Basement membrane heparan sulfate proteoglycans are concentrated in the laminae rarae and in podocytes of the rat renal glomerulus. Proc Natl Acad Sci U S A. 1985 May;82(10):3296–3300. doi: 10.1073/pnas.82.10.3296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stow J. L., Soroka C. J., MacKay K., Striker L., Striker G., Farquhar M. G. Basement membrane heparan sulfate proteoglycan is the main proteoglycan synthesized by glomerular epithelial cells in culture. Am J Pathol. 1989 Oct;135(4):637–646. [PMC free article] [PubMed] [Google Scholar]
  29. Timpl R., Dziadek M. Structure, development, and molecular pathology of basement membranes. Int Rev Exp Pathol. 1986;29:1–112. [PubMed] [Google Scholar]
  30. Timpl R. Recent advances in the biochemistry of glomerular basement membrane. Kidney Int. 1986 Sep;30(3):293–298. doi: 10.1038/ki.1986.183. [DOI] [PubMed] [Google Scholar]
  31. Timpl R., Wick G., Gay S. Antibodies to distinct types of collagens and procollagens and their application in immunohistology. J Immunol Methods. 1977;18(1-2):165–182. doi: 10.1016/0022-1759(77)90168-5. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES