Store-Operated Ca²⁺ Entry (SOCE) contributes to angiotensin II-induced cardiac fibrosis in cardiac fibroblasts

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• 作者：Boyu Zhang^a ; Jianmin Jiang^a ; Zhongbao Yue^a ; Shenglan Liu^a ; Yunzi Ma^a ; Na Yu^a ; Ying Gao^a ; Shuya Sun^a ; Shaorui Chen^a ; ^{chshaor@mail.sysu.edu.cn} ; Peiqing Liu^a ; ^b ; ^c ; ^d ; ^{liupq@mail.sysu.edu.cn}
• 关键词：Cardiac fibrosis ; Store-operated Ca2+ entry ; Angiotensin II ; Stromal interaction molecule1 ; Orai1
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：132
• 期：3
• 页码：171-180
• 全文大小：2322 K
• 卷排序：132

文摘

Store-operated Ca2+ entry (SOCE) is an important mechanism of extracellular Ca2+ entry into cells. It has been proved that SOCE is involved in many pathologic and physiological processes. Two key participants of SOCE, stromal interaction molecule1 (STIM1) and Orai1, have been identified. But their function in cardiac fibroblasts remains elusive. In present study, our findings suggested the expression of STIM1 and Orai1 were increased followed by angiotensin II (Ang II) stimulation in vivo and in vitro. In cultured adult rat cardiac fibroblasts, Ang II led to STIM1 interact with Orai1 and Ca2+ release from intracellular calcium store. In addition, the upregulation of fibronectin (FN), connective tissue growth factor (CTGF) and smooth muscle α-actin (α-SMA) induced by Ang II were attenuated by SOCE inhibitor SKF-96365, similar results were observed by knocking down STIM1 and Orai1. Furthermore, we found that silencing Orai1 by RNA interference also suppressed the translocation of Nuclear Factor of Activated T-cells (NFAT) Isoforms NFATc4 and decreased the phosphorylation of Smad2 and Smad3 induced by Ang II. These results unraveled a novel role of SOCE as a key modulator in the Ang II-induced cardiac fibrosis by mediating Ca2+ influx.