{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:08:43Z","timestamp":1772158123650,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), an important endogenous gasotransmitter, is involved in the modulation of gastrointestinal motility, but whether it mediates the intestinal dysmotility in irritable bowel syndrome (IBS) is not known. This study explored the significance of cystathionine\u2010\u03b2\u2010synthase (CBS)\/H<jats:sub>2<\/jats:sub>S signaling in stress\u2010induced colonic dysmotility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A rat model of IBS was established using chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically. Intestinal motility was determined by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was assessed using the visceromotor response (VMR) to colorectal distension (CRD). Real\u2010time PCR, Western blotting, and immunostaining were performed to identify the expression of CBS in the colon. The contractions of distal colon were studied in an organ bath system and H<jats:sub>2<\/jats:sub>S content was measured by ELISA. The effects of SAM, a selective CBS activator, on colonic dysmotility were examined. MEK1 was tested as a potential upstream effector of CBS\/H<jats:sub>2<\/jats:sub>S loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>After 10\u2009days of WAS, the ITT was decreased and FWC was increased, and the VMR magnitude in response to CRD was enhanced. The colonic CBS expression and H<jats:sub>2<\/jats:sub>S levels were significantly declined in WAS\u2010exposed rats, and the density of CBS\u2010positive enteric neurons in the myenteric plexus in WAS\u2010treated rats was lower than that in controls. SAM treatment relieved WAS\u2010induced colonic hypermotility via increased H<jats:sub>2<\/jats:sub>S production. AZD6244, a selective inhibitor of MEK1, partially reversed CBS downregulation and colonic hypermotility in WAS\u2010treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Decreased CBS\/H<jats:sub>2<\/jats:sub>S signaling through increased MEK1 signaling might be important in the pathogenesis of chronic stress\u2010induced colonic hypermotility. SAM could be administered for disorders associated with intestinal hypermotility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14488","type":"journal-article","created":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T14:06:10Z","timestamp":1668348370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dysregulated cystathionine\u2010\u03b2\u2010synthase\/hydrogen sulfide signaling promotes chronic stress\u2010induced colonic hypermotility in rats"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-6633","authenticated-orcid":false,"given":"Mengjuan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Key Laboratory of Hubei Province for Digestive System Diseases  Wuhan 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