{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:00Z","timestamp":1789194600729,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>\n                    Evidence supports an important role of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release-activated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel protein\u00a01 (Orai1)-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in the development of renal fibrosis, a common pathologic feature of CKDs that lead to ESRD, but the molecular mechanisms remain unclear. We determined the role of Orai1 calcium channel in renal fibrosis induced by high-fat diet and by unilateral ureteral obstruction. Mouse kidneys with fibrosis had higher levels of Orai1 protein expression than did kidneys without fibrosis.\n                    <jats:italic toggle=\"yes\">In\u00a0vivo<\/jats:italic>\n                    knockdown of Orai1 with adenovirus harboring Orai1\u2013short hairpin RNA or inhibition of Orai1 with SKF96365 dramatically prevented renal fibrosis and significantly decreased protein expression of fibronectin,\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    \u2011smooth muscle actin, and TGF\u2011\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    1 in the kidney cortex of ApoE\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice on a high-fat diet and in the obstructed kidneys of mice with unilateral ureteral obstruction. Compared with kidney biopsy specimens of patients with glomerular minimal change disease, those of patients with fibrotic nephropathy had higher expression levels of Orai1. In cultured human proximal tubule epithelial cells (HK2), knockdown of Orai1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel with adenovirus\u2013Orai1\u2013short hairpin RNA markedly inhibited TGF-\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    1\u2013induced intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and phosphorylation of smad2\/3. Knockdown or blockade of the Orai1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel in HK2 cells also prevented epithelial-to-mesenchymal transition induced by TGF\u2011\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    1. In conclusion, blockade of the Orai1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel prevented progression of renal fibrosis in mice, likely by suppressing smad2\/3 phosphorylation and TGF-\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    1\u2013induced epithelial-to-mesenchymal transition. These results render the Orai1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel a potential therapeutic target against renal fibrosis.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015080889","type":"journal-article","created":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T13:23:40Z","timestamp":1475241820000},"page":"3063-3078","source":"Crossref","is-referenced-by-count":60,"title":["Blockade of Orai1 Store-Operated Calcium Entry Protects against Renal Fibrosis"],"prefix":"10.1681","volume":"27","author":[{"given":"Xiaoyi","family":"Mai","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beixin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfei","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinling","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaguo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center 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