文章基本信息

标题：RGS12 Is a Novel Critical NF-κB Activator in Inflammatory Arthritis
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作者：Gongsheng Yuan ; Shuting Yang ; Andrew Ng 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-40
DOI：10.1016/j.isci.2020.101172
语种：English
出版社：Elsevier
摘要：SummaryRheumatoid arthritis (RA) is the most common inflammatory disease, which currently lacks effective treatment. Here, we discovered that the Regulator of G Protein Signaling 12 (RGS12) plays a key role in regulating inflammation. Transcriptional and protein analysis revealed that RGS12 was upregulated in human and mouse RA macrophages. Deletion of RGS12 in myeloid lineage or globally inhibits the development of collagen-induced arthritis including joint swelling and bone destruction. Mechanistically, RGS12 associates with NF-κB(p65) to activate its phosphorylation and nuclear translocation through PTB domain, and NF-κB(p65) regulates RGS12 expression in a transcriptional manner. The nuclear translocation ability of NF-κB(p65) and RGS12 can both be enhanced by cyclooxygenase-2 (COX2). Furthermore, ablation of RGS12 via RNA interference significantly blocks the inflammatory processin vivoandin vitro. These results demonstrate that RGS12 plays a critical role in the pathogenesis of inflammatory arthritis.Graphical AbstractDisplay OmittedHighlights•RGS12 regulates inflammation through activating an RGS12-NF-κB positive feedback loop•RGS12 activates NF-κB nuclear translocation and phosphorylation•PTB domain of RGS12 promotes the association of RGS12 and NF-κB•COX2 enhances nuclear translocation of RGS12/NF-κB in inflammatory conditionsOrthopedics Immunology; Transcriptomics