title: Tumor necrosis factor-α regulates matrix metalloproteinase-2 expression and cell migration via ERK pathway in rat glomerular mesangial cells.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Yuebing
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Ningning
authors.initials: N
authors.lastname: He
authors.forename: Liang
authors.initials: L
authors.lastname: Leng
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: extracellular signal-regulated kinase; glomerulus; matrix metalloproteinase; mesangial cells; nuclear factor-kappaB; tumor necrosis factor-α