{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:39:45Z","timestamp":1792895985744,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670489"],"award-info":[{"award-number":["81670489"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Enterochromaffin (EC) cells have been associated with functional gastrointestinal disorders such as IBS. Recently, we found that glial cell\u2010derived neurotrophic factor (GDNF)\u2010rearranged during transfection (RET) localized in EC cells in human colonic epithelia. Here, we examine the role of GDNF\u2010RET in the pathophysiology of diarrhoea\u2010predominant irritable bowel syndrome (IBS\u2010D).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>GDNF was assessed by ELISA and immunohistochemistry in biopsies from IBS\u2010D patients and healthy controls. Stress was induced by using a wrap\u2010restraint stress (WRS) procedure to serve as an acute stress\u2010induced IBS model. The function of GDNF\u2010RET axis to intestinal stem cell (ISC) homeostasis, and EC cell numbers were assessed in vivo and in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GDNF\u2010RET was expressed in EC cells in human colon. GDNF was significantly increased in IBS\u2010D patients. WRS mice showed increased GDNF\u2010RET levels in colon. WRS induced visceral hypersensitivity by expanding of ISC and differentiation of EC cell via GDNF\u2010RET. Furthermore, GDNF\u2010treated mice recapitulated the phenotype of WRS mice. In vitro, GDNF treatment amplified Wnt signal and increased serotonin levels in colonic organoids in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified GDNF\u2010RET was presented in colonic epithelium of patients with IBS\u2010D. GDNF\u2010RET played important roles in regulating ISC and EC cell differentiation. Our findings, thus, provide RET inhibitor as new therapeutic targets for treatment of patients with IBS\u2010D.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12889","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T12:34:33Z","timestamp":1598618073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Acute stress disrupts intestinal homeostasis via GDNF\u2010RET"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-3070","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Qilu Hospital Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Laboratory of Translational Gastroenterology Qilu Hospital Cheeloo College of Medicine Shandong University  Jinan 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