RRC ID |
69790
|
Author |
Chang TK, Zhong YH, Liu SC, Huang CC, Tsai CH, Lee HP, Wang SW, Hsu CJ, Tang CH.
|
Title |
Apelin Promotes Endothelial Progenitor Cell Angiogenesis in Rheumatoid Arthritis Disease via the miR-525-5p/Angiopoietin-1 Pathway.
|
Journal |
Front Immunol
|
Abstract |
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.
|
Volume |
12
|
Pages |
737990
|
Published |
2021-1-1
|
DOI |
10.3389/fimmu.2021.737990
|
PMID |
34659230
|
PMC |
PMC8511637
|
MeSH |
3T3 Cells
Angiopoietin-1 / genetics
Angiopoietin-1 / metabolism*
Animals
Apelin / genetics
Apelin / metabolism*
Arthritis, Experimental / genetics
Arthritis, Experimental / metabolism*
Arthritis, Experimental / pathology
Arthritis, Experimental / prevention & control
Arthritis, Rheumatoid / genetics
Arthritis, Rheumatoid / metabolism*
Arthritis, Rheumatoid / pathology
Chick Embryo
Endothelial Progenitor Cells / metabolism*
Endothelial Progenitor Cells / pathology
Fibroblasts / metabolism*
Fibroblasts / pathology
Humans
Mice
MicroRNAs / genetics
MicroRNAs / metabolism*
Neovascularization, Pathologic*
RNA Interference
Signal Transduction
Synoviocytes / metabolism*
Synoviocytes / pathology
|
IF |
5.085
|
Resource |
Human and Animal Cells |
MH7A(RCB1512) |