{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:02:44Z","timestamp":1787500964918,"version":"build-2736575974"},"reference-count":196,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology\u2014both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB1 and CB2 receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.<\/jats:p>","DOI":"10.3390\/cells8111311","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"1311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-5911","authenticated-orcid":false,"given":"Pedro","family":"Melgar-Lesmes","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Department of Biomedicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-8337","authenticated-orcid":false,"given":"Meritxell","family":"Perramon","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9376-0214","authenticated-orcid":false,"given":"Wladimiro","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Department of Biomedicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","article-title":"Pathobiology of liver fibrosis: A translational success story","volume":"64","author":"Lee","year":"2015","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1365-2559.2011.04145.x","article-title":"The epidemiology, pathogenesis and histopathology of fatty liver disease","volume":"61","author":"Levene","year":"2012","journal-title":"Histopathology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. 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