{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:54:22Z","timestamp":1793120062404,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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","award":["81900514"],"award-info":[{"award-number":["81900514"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Hepatic fibrosis is a progressive response to chronic liver injury. A key event in the development of hepatic fibrosis is the activation of hepatic stellate cells (HSCs); emerging research indicates that microRNAs play crucial roles in regulating HSCs activation. However, the specific roles of miR\u2010126\u20103p (miR\u2010126) and miR\u2010195\u20105p (miR\u2010195) in liver fibrosis remain inadequately understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the expression of miR\u2010126 and miR\u2010195 in activated HSCs, fibrotic liver tissues from animal models, and blood samples from patients with liver disease. The effects on cell proliferation and migration were investigated by MTT, colony formation assay, cell wound healing assay, and Transwell assay. Finally, we evaluated the effect of miR\u2010126 and miR\u2010195 on the progression of liver fibrosis in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We revealed that miR\u2010126 and miR\u2010195 were markedly downregulated in activated HSCs, fibrotic liver tissues from animal models, and blood samples from patients with liver diseases. Functional experiments demonstrated that the overexpression of miR\u2010126 and miR\u2010195 significantly inhibited the proliferation, migration, and fibrotic markers expression in HSCs. Conversely, silencing miR\u2010126 and miR\u2010195 produced the opposite effects. Further mechanistic studies showed that miR\u2010126 and miR\u2010195 downregulate insulin receptor substrate 1 (IRS1) or phosphoinositide 3\u2010kinase regulatory subunit 2 (PIK3\u2010R2), respectively, thereby inhibiting the pro\u2010fibrotic signalling pathway (IRS1\/PI3K) and regulating the functions of HSCs. Importantly, in\u00a0vivo experiments demonstrated that miR\u2010126 and miR\u2010195 markedly alleviated CCL\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced hepatic fibrosis in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results unravel that miR\u2010126 and miR\u2010195 inhibit liver fibrosis by suppressing the IRS\/PI3K pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70302","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T12:14:41Z","timestamp":1756728881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>MiR<\/scp>\n                    \u2010126\u20103p and\n                    <scp>MiR<\/scp>\n                    \u2010195\u20105p as Novel Therapeutic Attenuators of Liver Fibrosis by Targeting the\n                    <scp>IRS1<\/scp>\n                    \/\n                    <scp>PI3K<\/scp>\n                    Signalling Pathway"],"prefix":"10.1111","volume":"45","author":[{"given":"Xia","family":"Yuan","sequence":"first","affiliation":[{"name":"Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology Chengdu Medical College  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, School of Bioscience and Technology Chengdu Medical College  Chengdu Sichuan People's Republic of China"},{"name":"The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Nanbu People's Hospital  Chengdu People's Republic of 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