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Growth hormone secretagogue receptor (GHSR) is the receptor of nutrient\u2010sensing hormone ghrelin that has essential functions in metabolism, inflammation, and wound\u2010healing. However, the role of GHSR in liver fibrosis is unknown. This study uses a carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2010induced liver fibrosis mouse model to investigate the role of macrophage GHSR in liver fibrosis. CCl\n                    <jats:sub>4<\/jats:sub>\n                    induces macrophage accumulation and inflammatory responses, noticeably increases GHSR expression in the liver. It is found that macrophage\n                    <jats:italic>Ghsr<\/jats:italic>\n                    deletion (\n                    <jats:italic>Ghsr\u2010M\u03d5KO<\/jats:italic>\n                    ) attenuates CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced liver fibrosis and inflammation, showing reduced hepatic monocyte\u2010derived macrophages (MDMs) and suppressed proinflammatory responses. In macrophages, transforming growth factor (TGF)\u2010\u03b21 expression is positively correlated with GHSR expression. GHSR\u2010associated TGF\u2010\u03b21 in macrophages activates hepatic stellate cells (HSCs) by promoting the crosstalk between macrophages and HSCs. Macrophage GHSR controls inflammation and TGF\u2010\u03b21 expression via protein kinase A (PKA)\u2010mediated Forkhead box protein O 1 (Foxo1) phosphorylation at S273; Foxo1\u2010S273D mutation, mimicking constitutive phosphorylation of Foxo1 at S273, shows exacerbated CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced liver inflammation and fibrosis. Thus, targeting the macrophage GHSR\u2212Foxo1 signaling may provide a new strategy to treat liver fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504223","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:08:22Z","timestamp":1749726502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["GHSR\u2010Foxo1 Signaling in Macrophages Promotes Liver Fibrosis via Inflammatory Response and Hepatic Stellate Cell Activation"],"prefix":"10.1002","volume":"12","author":[{"given":"Da Mi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University  College Station TX 77843 USA"},{"name":"Department of Veterinary Pathobiology Texas A&amp;M University  College Station TX 77843 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of 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