{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:03:09Z","timestamp":1790650989992,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Liver fibrosis (LF) is a major disease that threatens human health. Hepatic stellate cells (HSCs) contribute directly to LF via extracellular matrix (ECM) secretion. Moreover, RXR\u03b1 is an important nuclear receptor that plays a key regulatory role in HSC activation. Meanwhile, microRNAs (miRNAs) have been identified as significant regulators of LF development. In particular, miR-654-5p is involved in cellular migration and proliferation, and <jats:italic>via<\/jats:italic> bioinformatics analysis, has been identified as a potential factor that targets RXR\u03b1 in humans and in mice. However, the precise relationship between miR-654-5p and RXR\u03b1 in the context of LF, remains unknown and is the primary focus of the current study. To establish <jats:italic>in vitro<\/jats:italic> activated cell model human primary HSCs were cultured <jats:italic>in vitro<\/jats:italic> and LX-2 cells were stimulated with recombinant human TGF-\u03b21. mRNA and protein levels of RXR\u03b1, miR-654-5p and fibrogenic genes were compared in quiescent and activated HSCs. Moreover, after transfected with miR-654-5p mimics, the expression changes of above related genes in LX-2 cells were estimated. Meanwhile, cell proliferation and apoptosis were detected in miR-654-5p overexpressed LX-2 cells. Simultaneously, the targeted binding between miR-654-5p and RXR\u03b1 was verified in LX-2 cells. Carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced mouse model with liver fibrosis was use to research the role of the miR-654-5p <jats:italic>in vitro<\/jats:italic>. Our results show that miR-654-5p expression levels increased in activated human HSCs and TGF\u03b2-treated LX-2 cells. Moreover, miR-654-5p mimics markedly promoted LX-2 cell proliferation while inhibiting their apoptosis. Accordingly, the expression levels of RXR\u03b1 are decreased in activated HSCs and LX-2 cells. Additionally, dual-luciferase reporter assay results reveal direct targeting of RXR\u03b1 by miR-654-5p. Similarly, <jats:italic>in vivo<\/jats:italic> miR-654-5p overexpression aggravates LF in mice that are intraperitoneally injected with CCl<jats:sub>4<\/jats:sub>. Taken together, our findings elucidated a novel molecular mechanism with potential use for treatment of LF.<\/jats:p>","DOI":"10.3389\/fcell.2022.841248","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:25:12Z","timestamp":1649226312000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["miR-654-5p Contributes to the Activation and Proliferation of Hepatic Stellate Cells by Targeting RXR\u03b1"],"prefix":"10.3389","volume":"10","author":[{"given":"Heming","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1007\/s00210-020-01896-0","article-title":"Silencing of Tissue Factor by Antisense Deoxyoligonucleotide Mitigates Thioacetamide-Induced Liver Injury","volume":"393","author":"Abdel-Bakky","year":"2020","journal-title":"Naunyn-schmiedeberg's Arch. 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