分子生物学
化学
蛋白酶激活受体2
成纤维细胞生长因子受体
成纤维细胞生长因子
成纤维细胞生长因子受体4
表皮生长因子受体
FGF1型
癌症研究
交易激励
受体
成纤维细胞
作者
Abdelkarim Sabri,Jacob Short,Jianfen Guo,Susan F. Steinberg
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2002-09-20
卷期号:91 (6): 532-539
被引量:99
标识
DOI:10.1161/01.res.0000035242.96310.45
摘要
Proteases elaborated by inflammatory cells in the heart would be expected to drive cardiac fibroblasts to proliferate, but protease-activated receptor (PAR) function in cardiac fibroblasts has never been considered. This study demonstrates that PAR-1 is the only known PAR family member functionally expressed by cardiac fibroblasts and that PAR-1 activation by thrombin leads to increased DNA synthesis in cardiac fibroblasts. The increase in DNA synthesis induced by PAR-1 substantially exceeds the effects of other G protein- coupled receptor agonists in this cell type. PAR-1 stimulates phosphoinositide hydrolysis and mobilizes intracellular calcium via pertussis toxin (PTX)-sensitive and PTX-insensitive pathways. Activation of PAR-1 leads to an increase in Src, Fyn, and epidermal growth factor receptor (EGFR) phosphorylation, with EGFR receptor transactivation by Src family kinases the major mechanism for PAR-1- dependent activation of extracellular signal-regulated kinase, p38-mitogen-activated protein kinase, and protein kinase B. Activation of PAR-1 also leads to an increase in DNA synthesis. PAR-1 signaling is highly contextual in nature, inasmuch as PAR-1 activates extracellular signal-regulated kinase and only weakly stimulates protein kinase B via a pathway that does not involve EGFR transactivation in cardiomyocytes. PAR-1 responses in cardiac fibroblasts and cardiomyocytes are predicted to contribute importantly to remodeling during cardiac injury and/or inflammation. (Circ Res. 2002;91:532-539.)
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