Regulator of G protein signaling 12 drives inflammatory arthritis by activating synovial fibroblasts through MYCBP2/KIF2A signaling.

ABSTRACT: Synovial fibroblasts are the active and aggressive drivers in the progression of arthritis, but the cellular and molecular mechanisms remain unknown. Here, our results showed that regulator of G protein signaling 12 (RGS12) maintained ciliogenesis in synovial fibroblasts, which is critical for the development of inflammatory arthritis. Deletion of RGS12 led to a significant decrease in ciliogenesis, adhesion, migration, and secretion of synovial fibroblasts. Mechanistically, RGS12 overexpression in synovial fibroblasts increased the length and number of cilia but decreased the protein level of kinesin family member 2A (KIF2A). The results of LC-MS analyses showed that RGS12 interacted with MYC binding protein 2 to enhance its ubiquitination activity, through which the KIF2A protein was deg

SUBMITTER: Yuan G 

PROVIDER: S-EPMC9843488 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature