NFIC attenuates rheumatoid arthritis-induced inflammatory response in mice by regulating PTEN/SENP8 transcription

Abstract

ObjectiveTo explore whether nuclear factor I C (NFIC) alleviated inflammatory response of synovial fibroblasts (SFs) caused by rheumatoid arthritis (RA) by regulating transcription levels of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and sentrin-specific protease 8 (SENP8). MethodsNFIC, PTEN, and SENP8 levels in RASFs and normal SFs (NSFs) were measured by qRT-PCR and western blotting. The levels of Bax, Bcl-2, MMP-3, and MMP-13, as well as the content of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined in RASFs and NSFs using western blotting and ELISA. The binding of NFIC to promoter sequences of PTEN and SENP8 was predicted and verified. A mouse model of collagen-induced arthritis (CIA) was established and evaluated according to the degree of joint swelling and arthritis index. ResultsNFIC, PTEN, and SENP8 were downregulated in RASFs. RASFs had increased viability and MDA levels as well as decreased cell apoptosis and SOD content. NFIC was demonstrated to modulate the transcription of PTEN and SENP8 as their transcription factor. NFIC ameliorated the inflammatory response induced by RA in vivo by promoting the transcription of PTEN and SENP8. ConclusionNFIC acted as a transcription factor to facilitate the transcription of PTEN and SENP8, thereby inducing apoptosis of RASFs and effectively attenuating inflammatory response in CIA mice.