IL-1beta stimulates alpha-smooth muscle actin expression through JNK/p38 signal pathway in cultured rat mesangial cells.
- Author:
Yu WANG
1
;
Xiao-Mei LI
;
Hai-Yan WANG
Author Information
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
- Publication Type:Journal Article
- MeSH:
Actins;
biosynthesis;
Animals;
Cells, Cultured;
Glomerular Mesangium;
metabolism;
Interleukin-1;
pharmacology;
JNK Mitogen-Activated Protein Kinases;
MAP Kinase Kinase 4;
MAP Kinase Signaling System;
drug effects;
physiology;
Male;
Mitogen-Activated Protein Kinase Kinases;
drug effects;
physiology;
Mitogen-Activated Protein Kinases;
drug effects;
physiology;
Muscle, Smooth;
metabolism;
Rats;
Rats, Sprague-Dawley
- From:
Acta Physiologica Sinica
2002;54(3):244-250
- CountryChina
- Language:Chinese
-
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.
