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Effects of advanced glycosylation endproducts on perlecan core protein of glomerular epithelium

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Abstract

Perlecan is one of major heparan sulfate proteoglycans in the glomerular basement membrane and is reduced in the renal parenchyma of diabetic patients and animals with proteinuria. To examine the effects of glucose and advanced glycosylated end-products (AGE) on perlecan, we cultured rat glomerular epithelial cells (GEpC) on AGE- or bovine serum albumin (BSA)-coated plates under normal (NG, 5 mM) and high-glucose (HG, 30 mM) conditions and measured the change in perlecan core protein production by a sandwich ELISA and northern blot analysis. We observed significant decreases of perlecan core protein under HG conditions at 1 week incubation, specifically on the AGE-coated compared with the BSA-coated surface, by 22.2% and 4.7%, respectively. The expression of mRNA for perlecan promoter was decreased under HG conditions on AGE-coated surfaces by 19.7% at 2 days and 61.1% at 1 week. Even under NG condition, the expression of mRNA was reduced by 30% at 1 week if GEpC were grown on an AGE-coated surface. In conclusion, HG and AGE have an additive effect in reducing the production of perlecan core protein by GEpC in vitro. AGE had a greater effect than HG, implying that the inhibition of AGE formation may be more effective than short-term glucose control in the prevention of diabetic proteinuria.

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References

  1. Parving H-H, Osterby R, Anderson PW, Hsueh WA (1996) Diabetic nephropathy. In: Brenner BM (ed) Brenner and Rector’s the kidney. Saunders, Philadelphia, pp 1864–1892

  2. Sharma K, Ziyadeh FN (1997) Biochemical events and cytokine interactions linking glucose metabolism to the development of diabetic nephropathy. Semin Nephrol 17:80–92

    CAS  PubMed  Google Scholar 

  3. Vlassara H (1996) Protein glycation in the kidney: role in diabetes and aging. Kidney Int 49:1795–1804

    CAS  PubMed  Google Scholar 

  4. Tamsma JT, Van den Born J, Bruijn JA, Assmann KJM, Weening JJ, Berden JHM, Wieslander J, Schrama E, Hermans J, Veerkamp JH, Lemkes HHPJ, Van der Woude FJ (1994) Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane. Diabetologia 37:313–320

    Article  CAS  PubMed  Google Scholar 

  5. Kreisberg JI, Hoover RL, Karnovsky MJ (1978) Isolation and characterization of rat glomerular epithelial cells in vitro. Kidney Int 14:21–30

    CAS  PubMed  Google Scholar 

  6. Singh AK, Mo WA, Dunea G, Arruda JAL (1997) Effect of glycated proteins on the matrix of glomerular epithelial cells. J Am Soc Nephrol 9:802–810

    Google Scholar 

  7. Pegoraro AA, Singh AK, Arruda JAL, Dunea G, Bakir AA (2000) A simple method to detect an albumin permeability factor in the idiopathic nephrotic syndrome. Kidney Int 58:1342–1345

    Article  CAS  PubMed  Google Scholar 

  8. Kasinath BS, Grellier P, Terhune WC, Ghosh-Choudhury G, Maldonado R, Abboud S (1996) Regulation of basement membrane heparan sulfate proteoglycan core protein gene expression by high glucose medium in glomerular epithelial cells. J Cell Physiol 167:131–136

    Article  CAS  PubMed  Google Scholar 

  9. Ziyadeh FN (1993) The extracellular matrix in diabetic nephropathy. Am J Kidney Dis 22:736–744

    CAS  PubMed  Google Scholar 

  10. Parthasarathy N, Spiro RG (1982) Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes 31:738–741

    CAS  PubMed  Google Scholar 

  11. Shimomura H, Spiro RG (1987) Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes: decreased levels of heparan sulfate proteoglycan and laminin. Diabetes 36:374–381

    CAS  PubMed  Google Scholar 

  12. Makino H, Yamasaki Y, Haramoto T, Shikata K, Hironaka K, Ota Z, Kanwar YS (1993) Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy. Lab Invest 68:45–55

    CAS  PubMed  Google Scholar 

  13. Van den Born J, Van den Heuvel LPWJ, Bakker MAH, Veerkamp JH, Assmann KJM, Weening JJ, Berden JHM (1993) Distribution of GBM heparan sulfate proteoglycan core protein and side chains in human glomerular diseases. Kindey Int 43:454–463

    Google Scholar 

  14. Nerlich A, Schleicher E (1991) Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions. Am J Pathol 139:889–899

    CAS  PubMed  Google Scholar 

  15. Makino H, Ikeda S, Haramoto T, Ota Z (1992) Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy. Nephron 61:415–421

    CAS  PubMed  Google Scholar 

  16. Van den Born J, Van Kraats AA, Bakker MA, Assmann KJ, Van den Heuvel LP, Veerkamp JH, Berden JH (1995) Selective proteinuria in diabetic nephropathy in the rat is associated with a relative decrease in glomerular basement membrane heparan sulphate. Diabetologia 38:161–172

    Article  PubMed  Google Scholar 

  17. Karasawa R, Nishi S, Suzuki Y, Imai N, Arakawa M (1997) Early increase of chondroitin sulfate glycosaminoglycan in the glomerular basement membrane of rats with diabetic glomerulopathy. Nephron 76:62–71

    CAS  PubMed  Google Scholar 

  18. Fukui M, Nakamura T, Ebihara L Shirato I, Tomino Y, Koide H (1992) ECM gene expression and its modulation by insulin in diabetic rats. Diabetes 41:1520–1527

    CAS  PubMed  Google Scholar 

  19. Kofoed-Enevoldsen A, Noonan D, Deckert T (1993) Diabetes mellitus induced inhibition of glucosaminyl N -deacetylase: effect of short-term blood glucose control in diabetic rats. Diabetologia 36:310–315

    CAS  PubMed  Google Scholar 

  20. Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassell JR (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 39:196–203

    CAS  PubMed  Google Scholar 

  21. Van Det NF, Van den Born J, Tamsma JT, Verhagen NAM, Berden JHM, Bruijn JA, Daha MR, Van der Woude FJ (1996) Effects of high glucose on the production of heparan sulphate proteoglycan by human mesangial and glomerular visceral epithelial cells in vitro. Kidney Int 49:1079–1089

    PubMed  Google Scholar 

  22. Van Det NF, Verhagen NAM, Tamsma JT, Berden JHM, Bruijn JA, Daha MR (1997) Regulation of glomerular epithelial cell production of fibronectin and transforming growth factor-β by high glucose, not by angiotensin II. Diabetes 46:834–840

    PubMed  Google Scholar 

  23. Ha T-S, Duraisamy S, Faulkner JL, Kasinath BS (2004) Regulation of glomerular endothelial cell proteoglycans by glucose. J Korean Med Sci 19:245–252

    CAS  PubMed  Google Scholar 

  24. Raats CJ, Van den Born J, Berden JH (2000) Glomerular heparan sulfate alterations: mechanisms and relevance for proteinuria. Kidney Int. 57:385–400

    Google Scholar 

  25. Iozzo RV, Cohen IR, Grassel S, Murdoch AD (1994) The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J. 302:625–639

    Google Scholar 

  26. Brownlee M, Cerami A, Vlassara H (1988) Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318:1315–1321

    CAS  PubMed  Google Scholar 

  27. Vlassara H, Bucala R, Striker L (1994) Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 70:138–151

    CAS  PubMed  Google Scholar 

  28. Makino H, Shikata K, Kushiro M, Hironaka K, Yamasaki Y, Sugimoto H, Ota Z, Araki N, Horiuchi S (1996) Roles of advanced glycation end-products in the progression of diabetic nephropathy. Nephrol Dial Transplant 11 [Suppl 5]:76–80

  29. Yang CW, Vlassara H, Peten EP, He CJ, Striker GE, Striker LJ (1994) Advanced glycosylation endproducts up-regulate gene expression found in diabetic glomerular disease. Proc Natl Acad Sci U S A 91:9136–9140

    PubMed  Google Scholar 

  30. Striker LJ, Striker GE (1996) Administration of AGEs in vivo induces extracellular matrix gene expression. Nephrol Dial Transplant 11 [Suppl 5]:62–65

  31. Ha T-S, Barnes JL, Stewart JL, Ko CW, Miner JH, Abrahamson DR, Sanes JR, Kasinath BS (1999) Regulation of renal laminin in mice with type II diabetes. J Am Soc Nephrol 10:1931–1939

    Google Scholar 

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Acknowledgements

The authors thank Dr. Balakuntalam S. Kasinath for his kind help. This study was partly supported by a grant from the Korean Ministry of Health and Welfare (HMP-98-M-5–0053) and the Korea Science and Engineering Foundation (KOSEF, R01–2002–000–00251–0).

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Authors and Affiliations

  1. Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea

    Tae-Sun Ha & Chang-Ju Song

  2. Department of Pediatrics, College of Medicine, Pochon CHA University, Sungnam, Korea

    Joon-Ho Lee

  3. Department of Pediatrics, College of Medicine, Chungbuk National University, Gaesin-dong 48, Heungdeok-gu, 361–240, Cheongju, Korea

    Tae-Sun Ha

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  1. Tae-Sun Ha
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Correspondence to Tae-Sun Ha.

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Ha, TS., Song, CJ. & Lee, JH. Effects of advanced glycosylation endproducts on perlecan core protein of glomerular epithelium. Pediatr Nephrol 19, 1219–1224 (2004). https://doi.org/10.1007/s00467-004-1590-1

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  • DOI: https://doi.org/10.1007/s00467-004-1590-1

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