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

Content Provider	Springer Nature Link
Author	Liu, Senyan Li, Yuehong Zhao, Huiying Chen, Dong Huang, Qiang Wang, Suxia Zou, Wanzhong Zhang, Youkang Li, Xiaomei Huang, Haichang
Copyright Year	2006
Abstract	Tissue transglutaminase (tTG) is a Ca$^{2+}$-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.
Starting Page	9
Ending Page	17
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	284
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2006-02-14
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	focal and segmental glomerulosclerosis tissue transglutaminase MMP-9 fibronectin Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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