{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:44:08Z","timestamp":1790228648209,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T00:00:00Z","timestamp":1453939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The parasympathetic nervous system (PNS), via neurotransmitter acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non\u2010alcoholic steatohepatitis (NASH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary hHSC were analyzed for synthesis of endogenous ACh and acetylcholinesterase and gene expression of choline acetyltransferase and muscarinic ACh receptors (mAChR). Cell proliferation and fibrogenic markers were analyzed in hHSC exposed to ACh, atropine, mecamylamine, methoctramine, and 4\u2010diphenylacetoxy\u2010<jats:italic>N<\/jats:italic>\u2010methylpiperidine methiodide. mAChR expression was analyzed in human NASH scored for fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that hHSC synthesize ACh and acetylcholinesterase and express choline acetyltransferase and M1\u2013M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and phosphoinositide 3\u2010kinase and Mitogen\u2010activated protein kinase kinase (MEK) signaling pathways, as well as increased fibrogenic markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that ACh regulates hHSC activation via M2 and M3 mAChR involving the phosphoinositide 3\u2010kinase and MEK pathways <jats:italic>in vitro<\/jats:italic>. Finally, we provide evidence that the PNS may be involved in human NASH fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13085","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T13:10:10Z","timestamp":1439471410000},"page":"475-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Acetylcholine induces fibrogenic effects via M2\/M3 acetylcholine receptors in non\u2010alcoholic steatohepatitis and in primary human hepatic stellate cells"],"prefix":"10.1111","volume":"31","author":[{"given":"Maelle L","family":"Morgan","sequence":"first","affiliation":[{"name":"University College London, Institute for Liver and Digestive Health Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sigala","sequence":"additional","affiliation":[{"name":"University College London, Institute for Liver and Digestive Health Royal Free 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