RRC ID 72445
Author Huang CC, Law YY, Liu SC, Hu SL, Lin JA, Chen CJ, Wang SW, Tang CH.
Title Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p.
Journal Cells
Abstract 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.
Volume 10(10)
Published 2021-10-1
DOI 10.3390/cells10102627
PII cells10102627
PMID 34685605
PMC PMC8534315
MeSH Adiponectin / metabolism* Animals Arthritis, Experimental / metabolism Arthritis, Experimental / pathology Arthritis, Rheumatoid / genetics Arthritis, Rheumatoid / pathology* Bone and Bones / pathology Cattle Cell Line Chickens Down-Regulation Endothelial Progenitor Cells / metabolism* Fibroblasts / metabolism* Fibroblasts / pathology Humans Lentivirus / metabolism MAP Kinase Signaling System MicroRNAs / antagonists & inhibitors* MicroRNAs / genetics MicroRNAs / metabolism Models, Biological Neovascularization, Physiologic / genetics* Synovial Membrane / pathology* Vascular Endothelial Growth Factor A / metabolism*
IF 4.366
Human and Animal Cells MH7A(RCB1512)