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Sheng Li Xue Bao. 2002 Jun 25;54(3):244-50.

[IL-1beta stimulates alpha-smooth muscle actin expression through JNK/p38 signal pathway in cultured rat mesangial cells].

[Article in Chinese]

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1
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034 Xiao-Mei Li Institute of Nephrology, Peking University, Beijing 100034, China. renalbmu@public.bta.net.cn

Abstract

To investigate the role of intracellular mitogen activated protein kinase (MAPKs, ERK, JNK and p38) signal pathways in IL-1beta -stimulated alpha-smooth muscle actin (alpha-SMA) expression in rat mesangial cells (rMC), alpha-SMA-promoter gene was transfected into rMC by electro-perforation method and the promoter activity was assayed after IL-1beta (10 ng/ml) stimulation. Protein expression of alpha-SMA was assayed by Western blot. The results were compared between the groups stimulated by IL-1beta with or without PD98059 and SB203580, which are thought to block ERK and p38 pathway, respectively. Dominant-negative-JNKK plasmid was co-transfected in rMC to block JNK pathway. The spatial distribution of alpha-SMA and microfilament-like structure was observed by a confocal laser scanning microscope or an electric microscope. After 6 or 24 h of incubation with IL-1beta, rMC underwent a phenotypic change, which was represented by up-regulation of alpha-SMA promoter activity and protein expression. An increase in alpha-SMA and microfilament-like structure was found around the cell nucleus. Block of JNK and/or p38 pathway greatly inhibited IL-1beta -induced alpha-SMA expression, and the block of p38 pathway also suppressed the basal level of alpha-SMA expression. In contrast, ERK pathway had no influence on the process. It is, therefore, concluded that IL-1beta -stimulated expression of alpha-SMA is due to its protein synthesis and cytoskeleton re-organization in activated rMC. Intracellular signal regulation of alpha-SMA expression seems to be mediated mainly by JNK/p38 pathways, but ERK appears to have no effect on the process.

PMID:
12075473
[Indexed for MEDLINE]
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