The involvement of advanced glycation endproducts (AGEs) in renal injury of diabetic glomerulosclerosis: Association with phenotypic change in renal cells and infiltration of immune cells

Yonghui Mao, Tetsuya Ootaka, Takao Saito, Hiroshi Sato, Toshinobu Sato, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Background. Glycation of proteins is regarded as one of the major causes of the progression of diabetic nephropathy (DN) and of the phenotypic changes in glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC from DN. It thus is very important to study the interrelationships and interaction between these causes. Methods. The localization of advanced glycation endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was evaluated by immunohistochemical study in patients with DN. Results. Nε-(carboxymethyl)lysine (CML), α-smooth muscle actin (SMA), and low-molecular-weight caldesmon (L-CLD) were localized in the mesangial area in DN. The intensity of mesangial SMA and L-CLD expression was significantly correlated with the index of diabetic glomerulosclerosis (IDGS), while the expression of pentosidine was correlated with the IDGS and with 24-h urinary protein. Pentosidine was localized in glomerular basement membrane (GBM) only in DN and had a significant correlation with the mesangial expression of SMA and L-CLD. Pyrraline deposition on the tubular basement membrane, and the expression of SMA and L-CLD, and the infiltration of immune cells were observed in interstitial areas in DN. The intensity of L-CLD expression had a close relationship with pyrraline deposition and immune cell infiltration. The expression of SMA and L-CLD in interstitial areas was significantly correlated with the percent interstitial volume. Conclusions. AGEs are involved in renal injury in DN, and their effect is, at least in part, exercised via phenotypic changes in intrinsic renal cells and by the infiltration of immune cells.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalClinical and experimental nephrology
Volume7
Issue number3
DOIs
Publication statusPublished - 2003 Sep

Keywords

  • Advanced glycation endproducts
  • Diabetic nephropathy
  • L-caldesmon
  • Leukocytes
  • α-Smooth muscle actin

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

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