{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T19:36:12Z","timestamp":1779392172500,"version":"3.53.1"},"reference-count":73,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The intestinal ischemia\/reperfusion (I\/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I\/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein\u2013coupled estrogen receptor (GPER) could protect the intestine against I\/R injury and explored the mechanism. Adult male C57BL\/6 mice were subjected to intestinal I\/R injury by clamping (45 min) of the superior mesenteric artery followed by 4 h of intestinal reperfusion. Our results revealed that the selective GPER blocker abolished the protective effect of estrogen on intestinal I\/R injury. Selective GPER agonist G-1 significantly alleviated I\/R-induced intestinal mucosal damage, neutrophil infiltration, up-regulation of TNF-\u03b1 and cyclooxygenase-2 (Cox-2) expression, and restored impaired intestinal barrier function. G-1 could ameliorate the impaired crypt cell proliferation ability induced by I\/R and restore the decrease in villus height and crypt depth. The up-regulation of inducible nitric oxide synthase (iNOS) expression after I\/R treatment was attenuated by G-1 administration. Moreover, selective iNOS inhibitor had a similar effect with G-1 on promoting the proliferation of crypt cells in the intestinal I\/R model. Both GPER and iNOS were expressed in leucine-rich repeat containing G-protein coupled receptor 5 (Lgr5) positive stem cells in crypt. Together, these findings demonstrate that GPER activation can prompt epithelial cell repair following intestinal injury, which occurred at least in part by inhibiting the iNOS expression in intestinal stem cells (ISCs). GPER may be a novel therapeutic target for intestinal I\/R injury.<\/jats:p>","DOI":"10.1042\/cs20180919","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T19:25:16Z","timestamp":1548962716000},"page":"449-464","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Activation of G protein\u2013coupled estrogen receptor protects intestine from ischemia\/reperfusion injury in mice by protecting the crypt cell proliferation"],"prefix":"10.1042","volume":"133","author":[{"given":"Shiquan","family":"Chai","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanbing","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching Lab of Morphology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Ming","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Second Hospital of Shandong University, Jinan 250033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2341-3460","authenticated-orcid":false,"given":"Bing","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,2,8]]},"reference":[{"key":"2021113011093540600_B1","doi-asserted-by":"publisher","first-page":"e100","DOI":"10.1002\/bjs.9330","article-title":"Modern treatment of acute mesenteric ischaemia","volume":"101","author":"Acosta","year":"2014","journal-title":"Br. 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