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

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2627
Author(s):  
Chien-Chung Huang ◽  
Yat-Yin Law ◽  
Shan-Chi Liu ◽  
Sung-Lin Hu ◽  
Jun-An Lin ◽  
...  

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.

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Chun-Hao Tsai ◽  
Chao-Ju Chen ◽  
Chi-Li Gong ◽  
Shan-Chi Liu ◽  
Po-Chun Chen ◽  
...  

AbstractAngiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays important roles in several cellular functions such as infiltration, migration, and motility. We report significantly higher levels of CXCL13 expression in collagen-induced arthritis (CIA) mice compared with controls and also in synovial fluid from RA patients compared with human osteoarthritis (OA) samples. RA synovial fluid increased endothelial progenitor cell (EPC) homing and angiogenesis, which was blocked by the CXCL13 antibody. By interacting with the CXCR5 receptor, CXCL13 facilitated vascular endothelial growth factor (VEGF) expression and angiogenesis in EPC through the PLC, MEK, and AP-1 signaling pathways. Importantly, infection with CXCL13 short hairpin RNA (shRNA) mitigated EPC homing and angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with CIA. CXCL13 is therefore a novel therapeutic target for RA.


2015 ◽  
Vol 240 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Javier Rodríguez-Carrio ◽  
Mercedes Alperi-López ◽  
Patricia López ◽  
Sara Alonso-Castro ◽  
Santiago Rubén Carro-Esteban ◽  
...  

2009 ◽  
Vol 117 (10) ◽  
pp. 355-364 ◽  
Author(s):  
Gian Paolo Fadini ◽  
Mattia Albiero ◽  
Andrea Cignarella ◽  
Chiara Bolego ◽  
Christian Pinna ◽  
...  

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Kuo Chang ◽  
You-Han Zhong ◽  
Shan-Chi Liu ◽  
Chien-Chung Huang ◽  
Chun-Hao Tsai ◽  
...  

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA.


2019 ◽  
Vol 52 ◽  
pp. 537-544 ◽  
Author(s):  
Hsiang-Ping Lee ◽  
Po-Chun Chen ◽  
Shih-Wei Wang ◽  
Yi-Chin Fong ◽  
Chang-Hai Tsai ◽  
...  

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Matthew David Silverman ◽  
Christian S Haas ◽  
Ali M Rad ◽  
Ali S Arbab ◽  
Alisa E Koch

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