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In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here, we demonstrate that HSD17B13 forms liquid\u2013liquid phase separation (LLPS) around lipid droplets in the livers of MASH patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of the PAF receptor or STAT3 pathway inhibits the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbates western diet\/carbon tetrachloride-induced liver inflammation in Hsd17b13\u2212\/\u2212 mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.<\/jats:p>","DOI":"10.1093\/jmcb\/mjae018","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T01:15:35Z","timestamp":1714612535000},"source":"Crossref","is-referenced-by-count":12,"title":["HSD17B13 liquid\u2013liquid phase separation promotes leukocyte adhesion in chronic liver inflammation"],"prefix":"10.1093","volume":"16","author":[{"given":"Jing","family":"Ye","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manman","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University , Nanjing 210008 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0834-4601","authenticated-orcid":false,"given":"Xingxin","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"2024121907073733700_bib1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41575-020-00406-0","article-title":"Nonalcoholic fatty liver disease: another leap forward","volume":"18","author":"Abdelmalek","year":"2021","journal-title":"Nat. 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