{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:46:50Z","timestamp":1782992810957,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N41A680395"],"award-info":[{"award-number":["N41A680395"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002873","name":"Chulalongkorn University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Liver fibrosis is characterized by excessive collagen accumulation, the principal component of the extracellular matrix (ECM), produced by activated hepatic stellate cells (HSCs). While the catabolic role of mannose receptor C\u2010type 2 (MRC2) in binding and degradation of collagen is established, its role in regulating pro\u2010fibrotic signaling remains undefined. We investigated the novel, non\u2010canonical signaling function of the collagen receptor MRC2 as a regulator of HSC activation. Using doxycycline\u2010inducible knockdown and overexpression systems in human HSCs, we show that MRC2 deficiency enhances activation phenotypes, including proliferation, migration, contraction, and collagen overproduction. Conversely, MRC2 overexpression suppressed these effects. Transcriptomic analysis of MRC2 knockdown cells revealed a\u00a0pro\u2010fibrotic transcriptional shift, with enrichment of pathways related to ECM organization, collagen biosynthesis, and the PI3K\/AKT signaling axis. Mechanistically, MRC2 depletion induced transcriptional upregulation of ECM genes and components of the integrin\/PI3K\/AKT axis, accompanied by increased AKT phosphorylation. Pharmacological inhibition of either PI3K or integrins reversed ECM gene expression and collagen phenotypes induced by MRC2 depletion, establishing these pathways as required mediators. Our findings identify a novel, non\u2010canonical signaling function of MRC2 as a negative regulator of HSC activation.<\/jats:p>","DOI":"10.1002\/adbi.70133","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:06:54Z","timestamp":1780916814000},"source":"Crossref","is-referenced-by-count":0,"title":["MRC2 Links Collagen Turnover to Integrin\/PI3K\/AKT\u2010Driven Fibrogenesis"],"prefix":"10.1002","volume":"10","author":[{"given":"Nuchanart","family":"Suntornnont","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Medical Biochemistry Program Department of Biochemistry Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Center of Excellence in Hepatitis and Liver Cancer Faculty of Medicine Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-7713","authenticated-orcid":false,"given":"Jiranuwat","family":"Sapudom","sequence":"additional","affiliation":[{"name":"Laboratory for Immuno Bioengineering Research and Applications Division of Engineering New York University Abu Dhabi  Abu Dhabi UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-7376","authenticated-orcid":false,"given":"Chaiyaboot","family":"Ariyachet","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Medical Biochemistry Program Department of Biochemistry Faculty of Medicine Chulalongkorn University  Bangkok Thailand"},{"name":"Center of Excellence in Hepatitis and Liver Cancer Faculty of Medicine Chulalongkorn University  Bangkok 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