{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:37:05Z","timestamp":1790516225326,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,3,25]],"date-time":"2017-03-25T00:00:00Z","timestamp":1490400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81370511"],"award-info":[{"award-number":["81370511"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Natural Science Foundation of Guangdong Province","award":["S2013010016541"],"award-info":[{"award-number":["S2013010016541"]}]},{"name":"the Science and Technology Planning Projects of Guangzhou City","award":["201604020002"],"award-info":[{"award-number":["201604020002"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role for PGE\n 2<\/jats:sub>\n and its EP\n 4<\/jats:sub>\n receptor in the promotion of mucosal proliferation. However, whether \u03b2\u2010arrestin1 (\u03b2\u2010arr1), a well\u2010established mediator of GPCRs, is involved in the PGE\n 2<\/jats:sub>\n \/EP\n 4<\/jats:sub>\n receptor\u2010mediated mucosal proliferation complex in PHG remains unclear. The aim of the study was to investigate whether \u03b2\u2010arr1 participated in PGE\n 2<\/jats:sub>\n \/EP\n 4<\/jats:sub>\n receptor\u2010mediated mucosal proliferation by recruiting the Src\/EGF receptor (EGFR) complex to activate Akt\/proliferating cell nuclear antigen (PCNA) signalling in PHG.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Gastric mucosal proliferation was examined in patients with PHG and the PHG model of\n \u03b2\u2010arr1<\/jats:italic>\n \u2010knockout (\n \u03b2\u2010arr<\/jats:italic>\n 1\u2010KO) and\n \u03b2\u2010arr1<\/jats:italic>\n \u2010wild type (\n \u03b2\u2010arr1<\/jats:italic>\n \u2010WT) mice. The induction of \u03b2\u2010arr1 and EP\n 4<\/jats:sub>\n receptor expression and the Src\/EGFR signalling elements was investigated, and the mechanisms underlying PGE\n 2<\/jats:sub>\n \u2010regulated gastric mucosal proliferation were analysed.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Portal hypertension suppressed COX\u20101 but not COX\u20102, which was accompanied by a down\u2010regulation of PGE\n 2<\/jats:sub>\n generation and EP\n 4<\/jats:sub>\n receptor levels in the mucosa of patients with PHG. PGE\n 2<\/jats:sub>\n administration markedly promoted mucosal proliferation in a mouse model of PHG. Targeted deletion of\n \u03b2\u2010arr1<\/jats:italic>\n abolished PGE\n 2<\/jats:sub>\n \/EP\n 4<\/jats:sub>\n receptor\u2010mediated gastric proliferation in PHG by repressing the Src\/EGFR\/Akt\/PCNA signalling network.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n These results indicate that \u03b2\u2010arr1 regulates PGE\n 2<\/jats:sub>\n \/EP\n 4<\/jats:sub>\n receptor\u2010mediated mucosal proliferation by promoting activation of the Src\/EGFR\/Akt\/PCNA signalling pathway, and thus, this network is a potential therapeutic target for PHG.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.13752","type":"journal-article","created":{"date-parts":[[2017,2,18]],"date-time":"2017-02-18T04:32:41Z","timestamp":1487392361000},"page":"848-866","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["PGE\n 2<\/sub>\n \/EP\n 4<\/sub>\n receptor attenuated mucosal injury via \u03b2\u2010arrestin1\/Src\/EGFR\u2010mediated proliferation in portal hypertensive gastropathy"],"prefix":"10.1111","volume":"174","author":[{"given":"Siwei","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou 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