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This study aimed to investigate the role of PIM2 and its regulatory mechanisms in liver fibrosis using a CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced mouse model and a TGF\u2010\u03b21\u2010stimulated human HSC line (LX\u20102) model. The results showed that PIM2 expression was significantly upregulated in fibrotic liver tissue and a specific subset of activated HSCs. Functional experiments showed that PIM2 knockdown suppressed the activation, proliferation, and glycolysis of this specific HSC subset, whereas PIM2 overexpression promoted these processes. These effects were reversed by the glycolysis inhibitor 2\u2010DG. Mechanistically, NUDT21 downregulation promoted PIM2 expression by regulating alternative polyadenylation (APA), resulting in PIM2 3\u2032UTR shortening. Downstream, PIM2 activated the transcription factor CEBPB, which upregulated the transcription of the glucose transporter SLC2A1 and ultimately drove glycolysis. In line with these findings, PIM2 knockdown effectively attenuated liver fibrosis in mice. In conclusion, this study identifies PIM2 as a key driver of HSC activation and glycolysis within a distinct HSC subpopulation. PIM2 expression is regulated by NUDT21\u2010mediated APA, and its function is mediated via the CEBPB\/SLC2A1 axis, providing a potential novel therapeutic target for liver fibrosis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600255rr","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:19:24Z","timestamp":1779895164000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NUDT21<\/scp>\n                    Downregulation Promotes Liver Fibrosis by Activating the\n                    <scp>PIM2<\/scp>\n                    \u2010Mediated\n                    <scp>CEBPB<\/scp>\n                    \/\n                    <scp>SLC2A1<\/scp>\n                    Glycolytic Axis in Hepatic Stellate Cells"],"prefix":"10.1096","volume":"40","author":[{"given":"Ming","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated 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