Sodium propionate improves rheumatoid arthritis by inhibiting survivin mediated proliferation of fibroblast like synoviocytes by promoting miR-140-5p

Abstract

Background

Increased proliferation and impaired death of fibroblast-like synovial cells play an important role in the development of rheumatoid arthritis (RA). Survivin plays an important role in the prodromal stage and prognosis of RA and has been introduced as a biomarker of joint injury in RA patients. The purpose of this study was to explore whether propionate alleviates RA through miR-140-5p/survivin pathway.

Methods

The synovial tissues of RA patients were collected to detect the expression levels of miR-140-5p and survivin; normal human fibroblast-like synovial cells (HLSs) and RA fibroblast-like synovial cells (RA-FLSs) were cultured and treated with 10 mM of sodium propionate (SP), then the expressions of miR-140-5p and survivin, cell viability and apoptosis were detected; collagen induced arthritis (CIA) rat model was constructed and treated with SP, then the tissue inflammation level and the expression levels of miR-140-5p and Survivin were detected.

Results

The expression of miR-140-5p decreased in synovial tissues of RA patients and RA-FLSs cells, while the expression of survivin increased significantly in RA patients. SP promoted miR-140-5p expression and apoptosis in RA-FLSs cells and inhibited survivin expression and cell viability of RA-FLSs cells. In addition, miR-140-5p plays a protective role by targeting survivin. Importantly, in the CIA rat model, SP reduced joint inflammatory response, and the miR-140-5p inhibitor weakened the protective effect of SP.

Conclusion

SP can alleviate RA by promoting the expression of miR-140-5p and inhibiting the excessive proliferation and death impairment of RA-FLSs cells induced by survivin.

Keywords:

• Rheumatoid arthritis
• sodium propionate
• survivin
• miR-140-5p
• fibroblast like synoviocytes

Authors’ contributions

All authors contributed substantially to this manuscript. All authors read and approved the final manuscript. S Ma contributed majorly for this manuscript with participating in all the experiments and writing the manuscript. J Wang and F He participated primarily in all the experiments and data analysis; DC Zuo and FY Li contributed mainly to the assays of western blotting and RT-qPCR; HT Fan and ZJ Yin contributed majorly to the conduction of animal models; H Liang contributed majorly to the assays of flow cytometry. And Q Li contributed to conception and design this study and guided the writing of manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by grants from the Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (No. 2019FE001(-283)).