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Molecular and Cellular Biochemistry

, Volume 284, Issue 1–2, pp 9–17 | Cite as

Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats

  • Senyan Liu
  • Yuehong Li
  • Huiying Zhao
  • Dong Chen
  • Qiang Huang
  • Suxia Wang
  • Wanzhong Zou
  • Youkang Zhang
  • Xiaomei Li
  • Haichang HuangEmail author
Article

Abstract

Tissue transglutaminase (tTG) is a Ca2+-dependent enzyme which stabilizes the extracellular matrix (ECM) through post-translational modification, and may play an important role in the pathogenesis of focal and segmental glomerulosclerosis (FSGS). Here, we have investigated whether tTG contributes to the glomerular ECM expansion in the puromycin aminonucleoside (PAN)-injection-induced experimental rat model of FSGS. The localization and expression of tTG, MMP-9 gelatinase, and the ECM component fibronectin (FN) in kidneys was determined by immunohistochemistry and measured by semi-quantitative analysis. Protein levels of tTG and MMP-9 were also analyzed by Western blotting.In situtransglutaminase activity was assayed by measurement of incorporated substrate and the immunofluorescence staining for the cross-linking product, ε-(γ-glutamyl) lysine. Prominent proteinuria, a typical pathological feature of FSGS, was observed in PAN injection group rats. tTG immunoreactivity was located markedly in glomeruli and the levels of this protein in whole-kidney homogenates of PAN injection group rats were significantly increased (361± 106% control, P< 0.05). Similarly, transglutaminase activity and ε-(γ-glutamyl) lysine were also predominately located within glomeruli and were much more intense in the PAN-injected group than that in control animals. MMP-9 was also located primarily within glomeruli. In PAN-injected kidneys, protein levels of active MMP-9 were significantly reduced (59± 27% control, P< 0.01), while pro-MMP-9 levels increased (148± 42% control, P< 0.05). Remarkable expression of glomerular fibronectin (FN) was found in PAN injection group rats. Semi-quantitative analysis demonstrated this increased intensity of FN staining in the PAN-injected rats was 149± 23% of the control values (P< 0.05). Enhanced cross-linking of ECM by tissue transglutaminase and decreased degradation due to reduced active MMP-9 expression may be at least partially responsible for the deposition of FN within injured glomeruli in experimental FSGS.

Key words

focal and segmental glomerulosclerosis tissue transglutaminase MMP-9 fibronectin 

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Senyan Liu
    • 1
  • Yuehong Li
    • 1
  • Huiying Zhao
    • 1
  • Dong Chen
    • 1
  • Qiang Huang
    • 1
  • Suxia Wang
    • 1
  • Wanzhong Zou
    • 1
  • Youkang Zhang
    • 1
  • Xiaomei Li
    • 1
  • Haichang Huang
    • 2
    Email author
  1. 1.Division of NephrologyPeking University First HospitalBeijingChina
  2. 2.Division of NephrologyPeking University First HospitalBeijingChina

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