Accumulation of N(ε)-(carboxymethyl)lysine and changes in glomerular extracellular matrix components in Otsuka Long-Evans Tokushima Fatty rat: A model of spontaneous NIDDM

Masahiko Kushiro, Kenichi Shikata, Hikaru Sugimoto, Kazuyoshi Ikeda, Seikoh Horiuchi, Hirofumi Makino

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Increases in extracellular matrix (ECM) and changes in its components have been documented in the glomeruli of diabetic nephropathy. Advanced glycation end products formed by glycoxidation have been shown to induce the synthesis of ECM components and transforming growth factor beta (TGF-β), suggesting that advanced glycation end products may be involved in the etiology of imbalance of ECM components in diabetic glomerulosclerosis. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an inbred strain that spontaneously develops non-insulin-dependent diabetes mellitus which progresses to diabetic glomerulosclerosis. N(ε)-(carboxymethyl)lysine (CML) is known to be formed by glycoxidation. To clarify the involvement of glycoxidation in diabetic nephropathy, we examined the localization of CML, ECM components, and TGF-β1 in the glomeruli of OLETF rats. The amounts of α3(IV) collagen, type VI collagen, and fibronectin were significantly increased in the glomeruli of OLETF rats, whereas the heparan sulfate proteoglycan levels were decreased. After 6 months of age, CML levels were significantly increased in the mesangial area of the glomeruli in these animals. The overexpression of TGF-β1 preceded the increase in glomerular ECM components. The present study demonstrated that the accumulation of CML precedes the changes of glomerular ECM components in the glomeruli during the course of diabetic nephropathy, suggesting that glycoxidation may be one of the major causes of diabetic glomerulosclerosis.

Original languageEnglish
Pages (from-to)458-468
Number of pages11
JournalNephron
Volume79
Issue number4
DOIs
Publication statusPublished - Aug 28 1998

Keywords

  • Advanced glycation end products
  • Collagen
  • Diabetic nephropathy
  • Extracellular matrix
  • N(ε)-(carboxymethyl)lysine
  • OLETF rat
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)
  • Urology

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