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During liver fibrosis, hepatic stellate cells (HSCs) transform into a highly proliferative, activated state, producing various cytokines, chemokines, and ECM. However, the precise mechanisms that license HSCs into the highly proliferative state remain unclear. Cyclin\u2010dependent kinase 1 (CDK1) is a requisite event for the transition of the G1\/S and G2\/M phases in eukaryotic cells. In this study, it is demonstrated that CDK1 and its activating partners, Cyclin A2 and Cyclin B1, are upregulated in both liver fibrosis\/cirrhosis patient specimens and the murine hepatic fibrosis models, especially in activated HSCs. In vitro, CDK1 is upregulated in spontaneously activated HSCs, and inhibiting CDK1 with specific small\u2010molecule inhibitors (CGP74514A, RO\u20103306, or Purvalanol A) orshort\u00a0hairpin\u00a0RNAs\u00a0(shRNAs) resulted in HSC apoptosis and cell cycle arrest by regulating Survivin expression. Above all, it is illustrated that increased CDK1 expression licenses the HSCs into a highly proliferative state and can serve as a potential therapeutic target in liver fibrosis.<\/jats:p>","DOI":"10.1002\/adbi.202300403","type":"journal-article","created":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T09:40:20Z","timestamp":1702719620000},"source":"Crossref","is-referenced-by-count":3,"title":["Targeting Cyclin\u2010Dependent Kinase 1 Induces Apoptosis and Cell Cycle Arrest of Activated Hepatic Stellate Cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Xinmei","family":"Kang","sequence":"first","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuowei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silin","family":"Tu","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Cui","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Li","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Dong","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"},{"name":"Cell\u2010gene Therapy Translational Medicine Research Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"},{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5653-291X","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Biotherapy Centre the Third Affiliated Hospital Sun Yat\u2010sen University  600# Tianhe Road Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,16]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66369"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.036"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00169-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.049"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-005-1055-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.01.010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-5-11"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90164-A"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.170"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200909144"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm019"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.24.7215"},{"key":"e_1_2_10_14_1","first-page":"G857","volume":"265","author":"Albrecht J. 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