{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:19:59Z","timestamp":1787026799864,"version":"build-2736575974"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Liver fibrosis develops in response to chronic toxic or cholestatic injury, and is characterized by apoptosis of damaged hepatocytes, development of inflammatory responses, and activation of Collagen Type I producing myofibroblasts that make liver fibrotic. Two major cell types, Hepatic Stellate Cells (HSCs) and Portal Fibroblasts (PFs) are the major source of hepatic myofibroblasts. Hepatotoxic liver injury activates Hepatic Stellate Cells (aHSCs) to become myofibroblasts, while cholestatic liver injury activates both aHSCs and Portal Fibroblasts (aPFs). aPFs comprise the major population of myofibroblasts at the onset of cholestatic injury, while aHSCs are increasingly activated with fibrosis progression. Here we summarize our current understanding of the role of aPFs in the pathogenesis of cholestatic fibrosis, their unique features, and outline the potential mechanism of targeting aPFs in fibrotic liver.<\/jats:p>","DOI":"10.3389\/fmolb.2021.790032","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T05:54:28Z","timestamp":1639374868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The role of Mesothelin signaling in Portal Fibroblasts in the pathogenesis of cholestatic liver fibrosis"],"prefix":"10.3389","volume":"8","author":[{"given":"Hiroaki","family":"Fuji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinori","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Loomba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kisseleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1158\/1535-7163.MCT-14-0132","article-title":"Efficacy of RG7787, a Next-Generation Mesothelin-Targeted Immunotoxin, against Triple-Negative Breast and Gastric Cancers","volume":"13","author":"Alewine","year":"2014","journal-title":"Mol. 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