{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:06:52Z","timestamp":1789175212394,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274448"],"award-info":[{"award-number":["82274448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction\u2010associated steatohepatitis (MASH), are globally prevalent conditions with limited therapeutic options. While macrophage scavenger receptor 1 (MSR1) is implicated in lipid uptake and inflammation, its role in MASLD pathogenesis remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MSR1 expression was analyzed using public databases and diet\u2010induced animal models. Myeloid\u2010specific\n                      <jats:italic>Msr1<\/jats:italic>\n                      knockout (\n                      <jats:italic>Msr1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u0394M\u03c6<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice were generated to investigate the specific function of MSR1. In\u00a0vitro, oxidized low\u2010density lipoprotein (ox\u2010LDL)\u2010stimulated primary mouse hepatic macrophages and bone marrow\u2010derived macrophages were analyzed to explore potential mechanisms. Finally, an MSR1 inhibitor was employed to demonstrate therapeutic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MSR1 was upregulated in liver tissues and hepatic macrophages of MASLD\/MASH patients and mice.\n                      <jats:italic>Msr1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u0394M\u03c6<\/jats:italic>\n                      <\/jats:sup>\n                      mice exhibited significant attenuation of steatosis, inflammation, and fibrosis in comparison to wild\u2010type littermates. In\u00a0vitro, ox\u2010LDL induced MSR1 expression, triggering lipid accumulation and pro\u2010inflammatory cytokine release. Mechanistically,\n                      <jats:italic>Msr1<\/jats:italic>\n                      deficiency upregulated the antioxidant enzyme superoxide dismutase 3 (SOD3) by inhibiting the PI3K\/AKT\/FoxO3a pathway, and these protective effects were blunted by\n                      <jats:italic>Sod3<\/jats:italic>\n                      knockdown. Conversely,\n                      <jats:italic>Sod3<\/jats:italic>\n                      overexpression ameliorated metabolic inflammation. Notably, pharmacological inhibition of MSR1 by fucoidan markedly attenuated the progression of diet\u2010induced MASLD in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MSR1 promotes MASLD progression by mediating ox\u2010LDL uptake in hepatic macrophages, which in turn exacerbates hepatic inflammation and fibrosis via PI3K\/AKT\/FoxO3a\u2010dependent suppression of SOD3. Targeting MSR1 or its downstream pathway represents a promising novel therapeutic strategy for treating MASLD and MASH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70755","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:27:53Z","timestamp":1782710873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MSR1<\/scp>\n                    Drives\n                    <scp>MASLD<\/scp>\n                    Progression Via Disrupting\n                    <scp>FoxO3a<\/scp>\n                    \u2010\n                    <scp>SOD3<\/scp>\n                    Mediated Redox Balance in Liver Macrophages"],"prefix":"10.1111","volume":"46","author":[{"given":"Wei","family":"Sheng","sequence":"first","affiliation":[{"name":"Institute of Digestive Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai 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