{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:54Z","timestamp":1785411414380,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2025-I2M-TS-12"],"award-info":[{"award-number":["2025-I2M-TS-12"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2021-I2M-1-060"],"award-info":[{"award-number":["2021-I2M-1-060"]}]},{"name":"Sichuan Science and Technology Program","award":["2026NSFSC0571"],"award-info":[{"award-number":["2026NSFSC0571"]}]},{"name":"Sichuan Science and Technology Program","award":["2025ZNSFSC0678"],"award-info":[{"award-number":["2025ZNSFSC0678"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82102383"],"award-info":[{"award-number":["82102383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82400737"],"award-info":[{"award-number":["82400737"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82102383"],"award-info":[{"award-number":["82102383"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82400737"],"award-info":[{"award-number":["82400737"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We previously demonstrated that HBV promotes liver fibrosis through the enhanced production of pyruvate. Pyruvate kinase M2 (PKM2), a key enzyme in pyruvate metabolism, plays an important role in liver fibrogenesis. Recently, lactylation of PKM2 has been identified, which contributes to stabilize its catalytically active tetrameric conformation. Therefore, we hypothesize that PKM2 lactylation is involved in the regulation of HBV-induced liver fibrosis. In this study, we found that sera lactate levels were increased in CHB patients and HBV-Tg mice. Moreover, the lysine lactylation levels of proteins in liver tissues were significantly increased in the HBV-Tg mice. In LX2 cells, we found that pyruvate treatment significantly increased the profibrotic gene expression and lactylation level of PKM2, which promoted its tetramer-to-dimer transition, inhibited its pyruvate kinase activity, and facilitated its nuclear distribution. Through immunoprecipitation, we identified that pyruvate induced PKM2 lactylation at the K206 site. PKM2 knockdown or K206 mutation reduced PKM2 lactylation and abrogated the induction of profibrotic gene expression by pyruvate. Collectively, our findings indicate that HBV infection stimulated pyruvate production, which increased PKM2 lactylation at K206 to promote the expression of profibrogenic genes in HSCs, leading to liver fibrogenesis.<\/jats:p>","DOI":"10.3390\/pathogens15040431","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:05:36Z","timestamp":1776348336000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HBV-Induced Pyruvate Increases Lactylation of Pyruvate Kinase M2 (PKM2) at K206 to Promote Liver Fibrosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7009-6095","authenticated-orcid":false,"given":"Wenxian","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China"},{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China"},{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youmin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, Kidney Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianding","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, Kidney Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatology, The Second People\u2019s Hospital of Fuyang City, Fuyang 236015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xie","sequence":"additional","affiliation":[{"name":"The Hospital of Xidian Group, Xi\u2019an 710077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8907-0029","authenticated-orcid":false,"given":"Xiaoqiong","family":"Duan","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China"},{"name":"The Hospital of Xidian Group, Xi\u2019an 710077, China"},{"name":"The Joint Laboratory on Transfusion-Transmitted Diseases (TTDs) Between Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Nanning Blood Center, Nanning Blood Center, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41577-021-00549-4","article-title":"Immunobiology and pathogenesis of hepatitis B virus infection","volume":"22","author":"Iannacone","year":"2022","journal-title":"Nat. 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