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We hypothesize that Pkm2, as a key regulatory enzyme of glycolysis pathway, triggers the activation of macrophages (M\u03c6), which results in proinflammatory cytokine production during the arthritis progress. In this study, Pkm2 was found to be overexpressed in ED1-positive M\u03c6 in spleens and synovial tissues from arthritic rats via immunofluorescence, Western blotting, and quantitative RT-PCR. To reveal the role of Pkm2, Dark Agouti rats were treated with either Pkm2 enzyme inhibitor shikonin or the RNA interference plasmids of Pkm2 and negative control plasmids, respectively, via i.p. injection. Pkm2 intervention could alleviate the severity of pristane-induced arthritis in aspects of the macroscopic arthritis score, perimeter changes of midpaw, and the synovitis and destruction of the bone and cartilage as well as reduce the ED1 and p-Stat1\u2013positive cell population in rat synovial tissues. Silencing Pkm2 by RNA interference in classical activated rat and mouse M\u03c6 resulted in less Tnf-\u03b1, Il-1\u03b2 production via Stat1 signaling. Collectively, Pkm2 is highly expressed in ED1-positive M\u03c6 of spleens and synovial tissues from arthritic rats and promotes M\u03c6 activation via Stat1 signaling. Pkm2 might be a promising selective metabolic target molecule for rheumatoid arthritis treatment.<\/jats:p>","DOI":"10.4049\/jimmunol.1901021","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T19:44:32Z","timestamp":1591386272000},"page":"181-192","source":"Crossref","is-referenced-by-count":43,"title":["Upregulated PKM2 in Macrophages Exacerbates Experimental Arthritis via STAT1 Signaling"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-3776","authenticated-orcid":false,"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an 710061, Shaanxi ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Ministry of Education , Xi\u2019an 710061, Shaanxi 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