RGS12 Is a Novel Critical NF-κB Activator in Inflammatory Arthritis.
作者： Gongsheng Yuan , Shuting Yang , Andrew Ng , Chuanyun Fu , Merry Jo Oursler
DOI: 10.1016/J.ISCI.2020.101172
关键词: Arthritis 、 Regulator of G protein signaling 、 Inflammation 、 NF-κB 、 Chemistry 、 Inflammatory arthritis 、 RNA interference 、 Cancer research 、 Activator (genetics) 、 Downregulation and upregulation
摘要: Summary Rheumatoid arthritis (RA) is the most common inflammatory disease, which currently lacks effective treatment. Here, we discovered that Regulator of G Protein Signaling 12 (RGS12) plays a key role in regulating inflammation. Transcriptional and protein analysis revealed RGS12 was upregulated human mouse RA macrophages. Deletion myeloid lineage or globally inhibits development collagen-induced including joint swelling bone destruction. Mechanistically, associates with NF-κB(p65) to activate its phosphorylation nuclear translocation through PTB domain, regulates expression transcriptional manner. The ability can both be enhanced by cyclooxygenase-2 (COX2). Furthermore, ablation via RNA interference significantly blocks process in vivo in vitro. These results demonstrate critical pathogenesis arthritis.
harvard.edu
elsevier.com
sci-hub.se 参考文章(47)
Shuying Yang, Yi-Ping Li, Tongjun Liu, Xiaoning He, Xue Yuan, Chunyi Li, Jay Cao, Yunjung Kim, Mx1-Cre mediatedRgs12conditional knockout mice exhibit increased bone mass phenotype genesis. ,vol. 51, pp. 201- 209 ,(2013) , 10.1002/DVG.22373
Richard M. Pope, Apoptosis as a therapeutic tool in rheumatoid arthritis Nature Reviews Immunology. ,vol. 2, pp. 527- 535 ,(2002) , 10.1038/NRI846
Max L. Schiff, David P. Siderovski, J. Dedrick Jordan, Greg Brothers, Bryan Snow, Luc De Vries, Daniel F. Ortiz, María Diversé-Pierluissi, Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel Nature. ,vol. 408, pp. 723- 727 ,(2000) , 10.1038/35047093
Tarek A. Samad, Kimberly A. Moore, Adam Sapirstein, Sara Billet, Andrew Allchorne, Stephen Poole, Joseph V. Bonventre, Clifford J. Woolf, Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity Nature. ,vol. 410, pp. 471- 475 ,(2001) , 10.1038/35068566
I. Matsumoto, Arthritis Provoked by Linked T and B Cell Recognition of a Glycolytic Enzyme Science. ,vol. 286, pp. 1732- 1735 ,(1999) , 10.1126/SCIENCE.286.5445.1732
Bryan E. Snow, Randy A. Hall, Andrejs M. Krumins, Greg M. Brothers, Denis Bouchard, Carol Anne Brothers, Stephen Chung, Joan Mangion, Alfred G. Gilman, Robert J. Lefkowitz, David P. Siderovski, GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain Journal of Biological Chemistry. ,vol. 273, pp. 17749- 17755 ,(1998) , 10.1074/JBC.273.28.17749
S. You, S.-A. Yoo, S. Choi, J.-Y. Kim, S.-J. Park, J. D. Ji, T.-H. Kim, K.-J. Kim, C.-S. Cho, D. Hwang, W.-U. Kim, Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 111, pp. 550- 555 ,(2014) , 10.1073/PNAS.1311239111
Zhenqiang Yao, Lianping Xing, Brendan F. Boyce, NF-κB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism Journal of Clinical Investigation. ,vol. 119, pp. 3024- 3034 ,(2009) , 10.1172/JCI38716
David A. Tipton, Denise C. Gay, Vaughn A. DeCoster, Effect of a Cyclooxygenase‐2 Inhibitor on Interleukin‐1β–Stimulated Activation of the Transcription Factor Nuclear Factor‐Kappa B in Human Gingival Fibroblasts Journal of Periodontology. ,vol. 78, pp. 542- 549 ,(2007) , 10.1902/JOP.2007.060250
Maja Milanovic, Michael Kracht, M. Lienhard Schmitz, The cytokine-induced conformational switch of nuclear factor κB p65 is mediated by p65 phosphorylation. Biochemical Journal. ,vol. 457, pp. 401- 413 ,(2014) , 10.1042/BJ20130780