RGS12 Is a Novel Critical NF-κB Activator in Inflammatory Arthritis.

ABSTRACT: Rheumatoid 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). Further

SUBMITTER: Yuan G 

PROVIDER: S-EPMC7281782 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature