Inhibition of regulator of G protein signaling 10, aggravates rheumatoid arthritis progression by promoting NF-κB signaling pathway. (June 2021)

• Record Type: Journal Article
• Authors: Ren, Jie; Wei, Wei; Tan, Liangyu; Yang, Qin; Lu, Qiuyu; Ding, Handong; Yue, Yuan; Tian, Ye; Hao, Liang; Wang, Min; Li, Jinle
• Is Part Of: Molecular immunology. Volume 134(2021)
• Page Start: 236
• Page End: 246
• Publication Date: 2021-06
• Subjects: CIA collagen-induced arthritis -- ELISA enzyme-linked immunosorbent assay -- RA rheumatoid arthritis -- RGS regulators of G protein signaling -- WB western blot; Rheumatoid arthritis -- RGS10 -- NF-κB -- AAV -- Immune response -- Therapeutic target; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.03.024
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: RGS10 inhibition in the knees exacerbates the severity of CIA manifestation. RGS10 negatively regulates the NF-κB signaling pathway in CIA mouse model. RGS10 regulation demonstrated a feedback mechanism of inflammation in macrophages. Abstract: Rheumatoid arthritis (RA) is the most common inflammatory arthropathy, with evidence pointing to an immune-mediated etiology that propagates chronic inflammation. Although targeted immune therapeutics and aggressive treatment strategies have substantially improved, a complete understanding of the associated pathological mechanisms of the disease remains elusive. This study aimed at investigating whether regulator of G protein signaling 10 (RGS10) could affect rheumatoid arthritis (RA) pathology by regulating the immune response. A DBA/J1 mouse model of RA was established and evaluated for disease severity. RGS10 expression was inhibited by adeno-associated virus in vivo. Moreover, small interfering RNA was used to downregulate RGS10 expression in raw 264.7 cells in vitro . Results showed that RGS10 inhibition augmented RA severity, and attenuated the increase in expression of inflammatory factors. Furthermore, activated NF-κB signaling pathways were detected following RGS10 inhibition. These results revealed that RGS10 inhibition directly aggravated the RA pathological process by activating the NF-κB signaling pathway. Therefore, RGS10 is a promising novel therapeutic target for RA treatment with a potential clinical impact.