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This study investigates Mas signaling and neutrophil extracellular traps (NETs) in acute liver failure (ALF), aiming to elucidate their mechanisms. Male\n                    <jats:italic>Mas1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and wild\u2010type mice, aged 6\u20138 weeks, receive intraperitoneally injected with lipopolysaccharide (LPS)\/D\u2010galactosamine (D\u2010Gal) (L\/G) to study NETs formation. Hepatic Mas expression increases in WT\u2010L\/G mice, whereas systemic\n                    <jats:italic>Mas1<\/jats:italic>\n                    knockout significantly reduces L\/G\u2010induced NETs and hepatotoxicity. Antibiotics treatment and co\u2010housing (\n                    <jats:italic>Mas1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u2010L\/G and WT\u2010L\/G mice) experiments show that gut flora influences the disease phenotype in\n                    <jats:italic>Mas1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u2010L\/G mice. Fecal metabolite analysis suggests that mice may be protected by reduced deoxycholic acid (DCA) production in\n                    <jats:italic>Mas1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    activated hepatic farnesoid X receptor (FXR), suppressing sphingosine\u20101\u2010phosphate (S1P)\u2010dependent NETs. Additionally,\n                    <jats:italic>Mas1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    also activates the FXR\u2010S1P\u2010NETs axis in the liver by inhibiting SHP2. Single\u2010cell sequencing shows decreased interaction between endothelial cells and Cldn1\n                    <jats:sup>+<\/jats:sup>\n                    CD177\n                    <jats:sup>+<\/jats:sup>\n                    senescent neutrophils through Col4a1\u2010CD44. This inhibits S1P\u2010induced Raf signaling pathway activation and NETs formation. Mas signaling significantly impacts NETs formation, highlighting its potential as an anti\u2010inflammatory therapeutic target for ALF.\n                  <\/jats:p>","DOI":"10.1002\/advs.202411428","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T06:39:21Z","timestamp":1745649561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mas Signaling Potentiates Neutrophil Extracellular Traps Formation Induced by Endothelial Cells Derived S1P in Mice with Acute Liver Failure"],"prefix":"10.1002","volume":"12","author":[{"given":"Bo","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tongji Hospital School of Medicine Tongji University  Shanghai 200065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and 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