{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:42:11Z","timestamp":1789180931254,"version":"build-2803163510"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic sclerosis (SSc) is a multisystem autoimmune disorder that is characterized by inflammation and fibrosis in the skin and internal organs. Previous studies indicate that inflammatory cells and cytokines play essential roles in the pathogenesis of SSc; however, the mechanisms that underlie the inflammation-driven development of SSc are not fully understood. In this study, we show that response gene to complement 32 (RGC32) is abundantly expressed in mouse macrophages in the early stage of bleomycin-induced SSc. Importantly, RGC32 is required to induce the inflammatory response during the onset of SSc, because RGC32 deficiency in mice significantly ameliorates skin and lung sclerosis and inhibits the expression of inflammatory mediators inducible NO synthase (iNOS) and IL-1\u03b2 in macrophages. RGC32 appears to be a novel regulator for the differentiation of classically activated macrophages (M1 macrophages). IFN-\u03b3 and LPS stimulation induces RGC32 expression in primary peritoneal macrophages and bone marrow\u2013derived macrophages. RGC32 deficiency impairs the polarization of M1 macrophages and attenuates iNOS and IL-1\u03b2 production. Mechanistically, RGC32 interacts with NF-\u03baB proteins and promotes iNOS and IL-1\u03b2 expression by binding to their promoters. Collectively, our data reveal that RGC32 promotes the onset of SSc by regulating the inflammatory response of M1 macrophages, and it may serve as a promising therapeutic target for treating SSc.<\/jats:p>","DOI":"10.4049\/jimmunol.1701542","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T16:50:10Z","timestamp":1520268610000},"page":"2777-2785","source":"Crossref","is-referenced-by-count":24,"title":["RGC32 Promotes Bleomycin-Induced Systemic Sclerosis in a Murine Disease Model by Modulating Classically Activated Macrophage Function"],"prefix":"10.1093","volume":"200","author":[{"given":"Chenming","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-You","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Georgia , Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"2025030610143333000_r1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1346-8138.2009.00758.x","article-title":"Future treatments in systemic sclerosis","volume":"37","author":"Asano","year":"2010","journal-title":"J. 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