Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis.

Autor: Fan P; Department of Rheumatism and Immunology, Xi'an, China.; Department of Renal Transplantation, Center of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., He L; Department of Rheumatism and Immunology, Xi'an, China., Hu N; Department of Rheumatism and Immunology, Xi'an, China., Luo J; Department of Rheumatism and Immunology, Xi'an, China., Zhang J; Department of Rheumatism and Immunology, Xi'an, China., Mo LF; Department of Rheumatism and Immunology, Xi'an, China., Wang YH; Department of Rheumatism and Immunology, Xi'an, China., Pu D; Department of Rheumatism and Immunology, Xi'an, China., Lv XH; Department of Rheumatism and Immunology, Xi'an, China., Hao ZM; Department of Rheumatism and Immunology, Xi'an, China., Ding CH; University of Tasmania, Tasmania, Tasmania, Australia., Xue WJ; Department of Renal Transplantation, Center of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Li Y; Department of Renal Transplantation, Center of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Jazyk: angličtina
Zdroj: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2017; Vol. 42 (1), pp. 145-155. Date of Electronic Publication: 2017 May 12.
DOI: 10.1159/000477123
Abstrakt: Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22).
Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR.
Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group.
Conclusion: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.
(© 2017 The Author(s). Published by S. Karger AG, Basel.)
Databáze: MEDLINE