{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:31:26Z","timestamp":1783474286231,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF0702003"],"award-info":[{"award-number":["2021YFF0702003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-\u03b2-muricholic acid (T-\u03b2-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.<\/jats:p>","DOI":"10.3390\/ijms25063424","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T10:54:38Z","timestamp":1710759278000},"page":"3424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways"],"prefix":"10.3390","volume":"25","author":[{"given":"Qiuxia","family":"Lin","sequence":"first","affiliation":[{"name":"Laboratory of Hepatointestinal Diseases and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Gastroenterology & Hepatology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatointestinal Diseases and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Gastroenterology & Hepatology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyun","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatointestinal Diseases and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Gastroenterology & Hepatology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatointestinal Diseases and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Gastroenterology & Hepatology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJM199906173402407","article-title":"Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs","volume":"340","author":"Wolfe","year":"1999","journal-title":"N. 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