title: Store-Operated Ca2+Entry (SOCE) contributes to angiotensin II-induced cardiac fibrosis in cardiac fibroblasts.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Boyu
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Zhongbao
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Yunzi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China. Electronic address: chshaor@mail.sysu.edu.cn.
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, China; National and Local Joint Engineering Laboratory of Druggabilitiy Assessment and Evaluation, Sun Yat-sen University, Guangzhou 510006, Guangdong, China; Guangdong Provincial Engineering Laboratory of Druggability and New Drugs Evaluation, China; Guangzhou Key Laboratory of Druggability Assessment for Biologically Active Compounds, China. Electronic address: liupq@mail.sysu.edu.cn.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D000071740:ORAI1 Protein / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071737:Stromal Interaction Molecule 1 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D000804:Angiotensin II; D002118:Calcium
keywords: Angiotensin II; Cardiac fibrosis; Orai1; Store-operated Ca(2+) entry; Stromal interaction molecule1