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Here, the role of Zc3h12c in macrophages is characterized using Tnfrsf11a\n                    <jats:sup>Cre<\/jats:sup>\n                    \u2010Zc3h12c\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    mice. Both Tnfrsf11a and Zc3h12c are highly expressed in the kidney tissue from patients with chronic kidney disease and showed a positive association with an interstitial fibrosis score. Single cell RNA sequencing demonstrated abundant Tnfrsf11a expression in murine kidney macrophages and a correlation with the induction of chemokines, macrophage phagocytosis, and activation upon kidney injury. In various kidney injury models, Tnfrsf11a\n                    <jats:sup>Cre<\/jats:sup>\n                    \u2010Zc3h12c\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    mice suffered from more injury and inflammation in the kidney, characterized by an increase in Ccr2 positive leukocyte infiltration. Mechanistic in vitro studies revealed that Zc3h12c suppresses macrophage activation toward a pro\u2010inflammatory phenotype, modulates macrophage survival, migration, and phagocytosis. Both in silico and in vitro analysis indicated that Zc3h12c regulates the pro\u2010inflammatory cytokines\/chemokines and chemokine receptors expression and modulates the alternative splicing of pre\u2010mRNAs STAT1. Thus, macrophage\u2010derived Zc3h12c limits tissue inflammation and injury, potentially via alternate splicing of pre\u2010mRNAs.\n                  <\/jats:p>","DOI":"10.1002\/advs.202506707","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T21:40:25Z","timestamp":1755726025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage Zc3h12c Limits Tissue Inflammation and Injury via Alternative Splicing of Pre\u2010mRNA"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-584X","authenticated-orcid":false,"given":"Chenyu","family":"Li","sequence":"first","affiliation":[{"name":"Division of Nephrology Department of Medicine IV Hospital of the Ludwig\u2010Maximilians University  80336 Munich Germany"},{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University Qingdao 266005 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