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Tumor necrosis factor‐α regulates matrix metalloproteinase‐2 expression and cell migration via ERK pathway in rat glomerular mesangial cells
Author(s) -
Wang Yuebing,
Li Ming,
Xu Yang,
He Ningning,
Leng Liang,
Li Zongjin
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10298
Subject(s) - mapk/erk pathway , tumor necrosis factor alpha , signal transduction , matrix metalloproteinase , microbiology and biotechnology , mesangial cell , kinase , nf κb , cancer research , extracellular matrix , endocrinology , biology , medicine , chemistry , kidney
Mesangial cells (MCs), vascular smooth muscle‐derived cells, contribute to glomerular injury by generating a number of cytokines such as tumor necrosis factor‐α (TNF‐α). Matrix metalloproteinases (MMPs), regulated by various stimuli, are important in remodeling of glomerular ECM, which leads to a number of renal diseases. We investigated whether TNF‐α participated in the regulation of MMPs and explored signal pathways involved in TNF‐α‐induced MMPs expression in rat glomerular MCs. Western blot and RT‐qPCR results showed that treatment with TNF‐α significantly increased the expression of MMP‐2, but not MMP‐9 at both protein and mRNA levels in rat glomerular MCs. The extracellular signal‐regulated kinase (ERK) and nuclear factor‐kappaB (NF‐κB) signal pathways were activated by TNF‐α. Moreover, the activation of NF‐κB pathway in rat MCs was effectively inhibited by PD98059, specific inhibitor of ERK, suggesting a role for ERK in regulating NF‐κB function. PD98059 or NF‐κB signal pathway selective inhibitor Bay 11‐7082 effectively blocked TNF‐α‐induced expression of MMP‐2 in rat MCs, as determined by gene and protein expression. C‐jun N‐terminal kinase (JNK) signal pathway had no effect on TNF‐α‐induced expression of MMP‐2, even though it was also activated by TNF‐α in rat MCs. Furthermore, TNF‐α could induce the cell migration of rat MCs, whereas ERK signal pathway specific inhibitor PD98059 compromised the cell migration triggered by TNF‐α. Thus, TNF‐α upregulates the expression of MMP‐2 via activation of ERK‐dependent NF‐κB pathway in rat MCs, which may contribute to the cell migration of rat MCs.