{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T09:39:00Z","timestamp":1765445940650,"version":"3.46.0"},"reference-count":51,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400789"],"award-info":[{"award-number":["82400789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Renal fibrosis is a critical pathological hallmark of chronic kidney disease. Although nonalcoholic fatty liver disease (NAFLD) has been implicated in kidney disease progression, its specific role and underlying mechanisms in renal fibrosis remain poorly understood. This study aims to investigate these mechanisms by establishing a mouse model of renal fibrosis through unilateral ureteral obstruction (UUO) combined with a high\u2010fat diet\u2010induced NAFLD. Single\u2010cell RNA sequencing, untargeted metabolomics, flow cytometry, and immunofluorescence are performed, along with in vitro experiments involving primary renal macrophages and coculture models. It is demonstrated that NAFLD exacerbates renal fibrosis, as HFD\u2010induced hepatocytes release significant levels of ANGPTL8, which activates renal CCR2\n                    <jats:sup>+<\/jats:sup>\n                    PIRB\n                    <jats:sup>+<\/jats:sup>\n                    macrophages. These specialized macrophages disrupt linoleic acid metabolism and increase the production of inflammatory cytokines, aggravating renal fibrosis. In addition, CCR2\n                    <jats:sup>+<\/jats:sup>\n                    PIRB\n                    <jats:sup>+<\/jats:sup>\n                    macrophages promote the activation and proliferation of Th17 cells, which can further contribute to the worsening of renal fibrosis. Thus, the ANGPTL8\/PIRB\/ALOX5AP axis is a crucial signaling pathway between the liver and kidneys, and CCR2\n                    <jats:sup>+<\/jats:sup>\n                    PIRB\n                    <jats:sup>+<\/jats:sup>\n                    macrophages play a pivotal role in the progression of NAFLD\u2010induced renal fibrosis. These findings suggest potential therapeutic targets to treat NAFLD\u2010related renal fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509351","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:16:26Z","timestamp":1758791786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonalcoholic Fatty Liver Disease Exacerbates the Advancement of Renal Fibrosis by Modulating Renal CCR2\n                    <sup>+<\/sup>\n                    PIRB\n                    <sup>+<\/sup>\n                    Macrophages Through the ANGPTL8\/PIRB\/ALOX5AP Axis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6994-8667","authenticated-orcid":false,"given":"Shuqi","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Urology Shenzhen Hospital Southern Medical University Shenzhen Guangdong 518100 China"},{"name":"The Third 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