Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p

Cells

Shan-Chi Liu¹  Shih-Wei Wang²  Yat-Yin Law³  Jun-An Lin⁴  Chien-Chung Huang⁴  Chih-Hsin Tang⁴  Sung-Lin Hu⁴  Chao-Ju Chen⁴ 

[1] Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 65152, Taiwan;Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan;Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;School of Medicine, China Medical University, Taichung 40402, Taiwan;

关键词: adiponectin;    rheumatoid arthritis;    angiogenesis;    VEGF;    miR-106a-5p;   

DOI  :  10.3390/cells10102627

来源: DOAJ

【 摘 要 】

Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed.

【 授权许可】

Unknown