{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:01:16Z","timestamp":1783764076331,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072660"],"award-info":[{"award-number":["82072660"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072660"],"award-info":[{"award-number":["82072660"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver fibrosis is the repair process of abnormal connective tissue hyperplasia after liver damage caused by different causes. Inhibition of PI3K\/Akt signalling pathway can reduce the deposition of extracellular matrix, inhibit the proliferation of hepatic stellate cells (HSCs), and promote its apoptosis to achieve the purpose of therapy. This study aimed to investigate the effect of Idelalisib (PI3K inhibitor) on carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced liver fibrosis in mice. We used CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis mouse model in vivo and TGF\u2010\u03b21\u2010stimulated HSCs to evaluate the antifibrosis activity of Idelalisib. In vivo, Idelalisib significantly alleviated CCl<jats:sub>4<\/jats:sub>\u2010induced liver damage, collagen deposition, and hydroxyproline accumulation in mice. Immunohistochemistry and Western blot results showed that Idelalisib could significantly inhibit the expressions of COL1 and \u03b1\u2010SMA in a concentration\u2010dependent manner. In cell experiments, Idelalisib significantly inhibited the expressions of COL1, SMA, and p\u2010Smad3 in TGF\u2010\u03b2\u2010induced HSCs, thereby inhibiting HSC activation. Flow cytometry and Western blot results showed that Idelalisib significantly promoted TGF\u03b2\u2010induced apoptosis of HSCs after 48\u00a0h of administration, but had no significant effect after 24\u00a0h. Idelalisib promoted the apoptosis of activated HSCs by inhibiting the PI3K\/Akt\/FOXO3\u00a0signalling pathway. To further explore the mechanism by which Idelalisib inhibited PI3K, we predicted the miRNA targeting PI3K through the database and crossed it with the down\u2010regulated miRNA reported in liver fibrosis mice in the past five years. Finally, we identified miR\u2010124\u20103p and miR\u2010143\u20103p. We then demonstrated that Idelalisib significantly promoted miR\u2010124\u20103p and miR\u2010142\u20103p in vitro and in vivo. Dual\u2010luciferase report analysis showed that Idelalisib significantly inhibited luciferase activity but had no significant effect on the luc\u2010MUT transfection assay. Finally, we demonstrated that Idelalisib reversed the effects of miR\u2010124\u20103p inhibitor on the PI3K\/Akt\/FOXO3 asterisk pathway and caspase\u20103. Idelalisib has potential as a candidate drug for alleviating liver fibrosis.<\/jats:p>","DOI":"10.1111\/jcmm.17039","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T04:10:37Z","timestamp":1636344637000},"page":"11185-11197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Protective effect of Idelalisib on carbon tetrachloride\u2010induced liver fibrosis via microRNA\u2010124\u20103P\/phosphatidylinositol\u20103\u2010hydroxykinase signalling pathway"],"prefix":"10.1111","volume":"25","author":[{"given":"Xiaohe","family":"Li","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Key Laboratory of Molecular Drug Research Nankai University Tianjin China"},{"name":"High\u2010throughput Molecular Drug Screening Centre Tianjin International Joint Academy of Biomedicine Tianjin 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