Regulation of TGF-β1-induced connective tissue growth factor expression in airway smooth muscle cells
Regulation of TGF-β1-induced connective tissue growth factor expression in airway smooth muscle cells
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DOI：
10.1152/ajplung.00156.2004
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发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Chung, KF
中科院分区：
文献类型：
--
作者：
Xie, SP;Sukkar, MB;Chung, KF
Transforming growth factor (TGF)-beta may play an important role in airway remodeling, and the fibrogenic effect of TGF-beta may be mediated through connective tissue growth factor (CTGF) release. We investigated the role of MAPKs and phosphatidylinositol 3-kinase (PI3K) and the effects of inflammatory cytokines on TGF-beta-induced CTGF expression in human airway smooth muscle cells (ASMC). We examined whether Smad signal was involved in the regulatory mechanisms. TGF-beta1 induced a time- and concentration-dependent expression of CTGF gene and protein as analyzed by real-time RT-PCR and Western blot. Inhibition of ERK and c-jun NH2-terminal kinase (JNK), but not of p38 MAPK and PI3K, blocked the effect of TGF-beta1 on CTGF mRNA and protein expression and on Smad2/3 phosphorylation. T helper lymphocyte 2-derived cytokines, IL-4 and IL-13, attenuated TGF-beta1-stimulated mRNA and protein expression of CTGF and inhibited TGF-beta1-stimulated ERK1/2 and Smad2/3 activation in ASMC. The proinflammatory cytokines tumor necrosis factor-alpha and IL-1beta reduced TGF-beta1-stimulated mRNA expression of CTGF but did not inhibit TGF-beta-induced Smad2/3 phosphorylation. TGF-beta1-stimulated CTGF expression is mediated by mechanisms involving ERK and JNK pathways and is downregulated by IL-4 and IL-13 through modulation of Smad and ERK signals.
