Skip to main content
NCBI home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1995 Apr;162(4):318–321.

Diabetic nephropathy. Mechanisms of mesangial matrix expansion.

C K Abrass 1
PMCID: PMC1022768  PMID: 7747496

Abstract

Diabetic nephropathy, a major cause of morbidity and mortality in patients with diabetes mellitus, is characterized by the progressive expansion of mesangial matrix that ultimately occludes glomerular capillaries. Multiple factors in the abnormal metabolic milieu of diabetes contribute to the development of increased amounts of mesangial matrix. Glucose stimulates an increase in synthesis of most collagens and matrix glycoproteins normally expressed within the mesangium. Abnormal glycosylation of matrix proteins interferes with their degradation and turnover. Periods of hyperinsulinemia and alterations in angiotensin II induce changes in the phenotype of mesangial cells and the composition of matrix they secrete. Together, glucose, insulin, and angiotensin II conspire to produce an unrelenting increase in accumulation of mesangial matrix, with altered composition and function.

Full text

PDF
318

Selected References

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

  1. 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]
  2. Abrass C. K., Raugi G. J., Gabourel L. S., Lovett D. H. Insulin and insulin-like growth factor I binding to cultured rat glomerular mesangial cells. Endocrinology. 1988 Nov;123(5):2432–2439. doi: 10.1210/endo-123-5-2432. [DOI] [PubMed] [Google Scholar]
  3. Abrass C. K., Spicer D., Raugi G. J. Induction of nodular sclerosis by insulin in rat mesangial cells in vitro: studies of collagen. Kidney Int. 1995 Jan;47(1):25–37. doi: 10.1038/ki.1995.3. [DOI] [PubMed] [Google Scholar]
  4. Abrass C. K., Spicer D., Raugi G. J. Insulin induces a change in extracellular matrix glycoproteins synthesized by rat mesangial cells in culture. Kidney Int. 1994 Sep;46(3):613–620. doi: 10.1038/ki.1994.313. [DOI] [PubMed] [Google Scholar]
  5. Anderson S. S., Tsilibary E. C., Charonis A. S. Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular basement membrane. J Clin Invest. 1993 Dec;92(6):3045–3052. doi: 10.1172/JCI116929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ausiello D. A., Kreisberg J. I., Roy C., Karnovsky M. J. Contraction of cultured rat glomerular cells of apparent mesangial origin after stimulation with angiotensin II and arginine vasopressin. J Clin Invest. 1980 Mar;65(3):754–760. doi: 10.1172/JCI109723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ayo S. H., Radnik R. A., Glass W. F., 2nd, Garoni J. A., Rampt E. R., Appling D. R., Kreisberg J. I. Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium. Am J Physiol. 1991 Feb;260(2 Pt 2):F185–F191. doi: 10.1152/ajprenal.1991.260.2.F185. [DOI] [PubMed] [Google Scholar]
  8. Ayo S. H., Radnik R., Garoni J. A., Troyer D. A., Kreisberg J. I. High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures. Am J Physiol. 1991 Oct;261(4 Pt 2):F571–F577. doi: 10.1152/ajprenal.1991.261.4.F571. [DOI] [PubMed] [Google Scholar]
  9. Bruneval P., Foidart J. M., Nochy D., Camilleri J. P., Bariety J. Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus. Hum Pathol. 1985 May;16(5):477–484. doi: 10.1016/s0046-8177(85)80086-1. [DOI] [PubMed] [Google Scholar]
  10. Danne T., Spiro M. J., Spiro R. G. Effect of high glucose on type IV collagen production by cultured glomerular epithelial, endothelial, and mesangial cells. Diabetes. 1993 Jan;42(1):170–177. doi: 10.2337/diab.42.1.170. [DOI] [PubMed] [Google Scholar]
  11. Delafontaine P., Lou H. Angiotensin II regulates insulin-like growth factor I gene expression in vascular smooth muscle cells. J Biol Chem. 1993 Aug 5;268(22):16866–16870. [PubMed] [Google Scholar]
  12. Gilbert R. E., Tsalamandris C., Bach L. A., Panagiotopoulos S., O'Brien R. C., Allen T. J., Goodall I., Young V., Seeman E., Murray R. M. Long-term glycemic control and the rate of progression of early diabetic kidney disease. Kidney Int. 1993 Oct;44(4):855–859. doi: 10.1038/ki.1993.322. [DOI] [PubMed] [Google Scholar]
  13. Haralson M. A., Jacobson H. R., Hoover R. L. Collagen polymorphism in cultured rat kidney mesangial cells. Lab Invest. 1987 Nov;57(5):513–523. [PubMed] [Google Scholar]
  14. Ikeda K., Kida H., Yokoyama H., Naito T., Takasawa K., Goshima S., Takeda S., Yoshimura M., Tomosugi N., Abe T. [Participation of collagen fibers in morphogenesis of diabetic nodular lesions]. Nihon Jinzo Gakkai Shi. 1988 Jul;30(7):843–853. [PubMed] [Google Scholar]
  15. Itoh H., Mukoyama M., Pratt R. E., Gibbons G. H., Dzau V. J. Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. J Clin Invest. 1993 May;91(5):2268–2274. doi: 10.1172/JCI116454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Juliano R. L., Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. doi: 10.1083/jcb.120.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kasiske B. L., Cleary M. P., O'Donnell M. P., Keane W. F. Effects of genetic obesity on renal structure and function in the Zucker rat. J Lab Clin Med. 1985 Nov;106(5):598–604. [PubMed] [Google Scholar]
  18. Kern T. S., Engerman R. L. Kidney morphology in experimental hyperglycemia. Diabetes. 1987 Feb;36(2):244–249. doi: 10.2337/diab.36.2.244. [DOI] [PubMed] [Google Scholar]
  19. Kim Y., Kleppel M. M., Butkowski R., Mauer S. M., Wieslander J., Michael A. F. Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol. 1991 Feb;138(2):413–420. [PMC free article] [PubMed] [Google Scholar]
  20. Kreisberg J. I., Ayo S. H. The glomerular mesangium in diabetes mellitus. Kidney Int. 1993 Jan;43(1):109–113. doi: 10.1038/ki.1993.18. [DOI] [PubMed] [Google Scholar]
  21. Lewis E. J., Hunsicker L. G., Bain R. P., Rohde R. D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993 Nov 11;329(20):1456–1462. doi: 10.1056/NEJM199311113292004. [DOI] [PubMed] [Google Scholar]
  22. Lin C. Q., Bissell M. J. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993 Jun;7(9):737–743. doi: 10.1096/fasebj.7.9.8330681. [DOI] [PubMed] [Google Scholar]
  23. Ling B. N., Seal E. E., Eaton D. C. Regulation of mesangial cell ion channels by insulin and angiotensin II. Possible role in diabetic glomerular hyperfiltration. J Clin Invest. 1993 Nov;92(5):2141–2151. doi: 10.1172/JCI116815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mauer S. M., Steffes M. W., Ellis E. N., Sutherland D. E., Brown D. M., Goetz F. C. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mohan P. S., Carter W. G., Spiro R. G. Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes. Diabetes. 1990 Jan;39(1):31–37. doi: 10.2337/diacare.39.1.31. [DOI] [PubMed] [Google Scholar]
  26. Pugliese G., Pricci F., Pugliese F., Mene P., Lenti L., Andreani D., Galli G., Casini A., Bianchi S., Rotella C. M. Mechanisms of glucose-enhanced extracellular matrix accumulation in rat glomerular mesangial cells. Diabetes. 1994 Mar;43(3):478–490. doi: 10.2337/diab.43.3.478. [DOI] [PubMed] [Google Scholar]
  27. Reddi A. S., Camerini-Davalos R. A. Diabetic nephropathy. An update. Arch Intern Med. 1990 Jan;150(1):31–43. [PubMed] [Google Scholar]
  28. Segal R., Fine L. G. Polypeptide growth factors and the kidney. Kidney Int Suppl. 1989 Nov;27:S2–10. [PubMed] [Google Scholar]
  29. 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]
  30. Steffes M. W., Osterby R., Chavers B., Mauer S. M. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes. 1989 Sep;38(9):1077–1081. doi: 10.2337/diab.38.9.1077. [DOI] [PubMed] [Google Scholar]
  31. Studer R. K., Craven P. A., DeRubertis F. R. Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes. 1993 Jan;42(1):118–126. doi: 10.2337/diab.42.1.118. [DOI] [PubMed] [Google Scholar]
  32. Wolf G., Haberstroh U., Neilson E. G. Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells. Am J Pathol. 1992 Jan;140(1):95–107. [PMC free article] [PubMed] [Google Scholar]
  33. Yamamoto T., Nakamura T., Noble N. A., Ruoslahti E., Border W. A. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1814–1818. doi: 10.1073/pnas.90.5.1814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yamamoto T., Noble N. A., Miller D. E., Border W. A. Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int. 1994 Mar;45(3):916–927. doi: 10.1038/ki.1994.122. [DOI] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES