Conditioned medium from human amnion⁃derived mesenchymal stem cells promotes angiogenesis through circRNA⁃0001649/miR⁃203a/VEGFA and miR⁃203a/MMP9 signaling pathway
Objective：This study aims to investigate whether conditioned medium from human amnion-derived mesenchymal stem cells（hAMSC-CM） promotes angiogenesis of human umbilical vein endothelial cells（HUVEC） via circRNA-0001649（circ-0001649）. Methods：HUVECs were divided into control group，conditioned medium stimulation group（CM-group），conditioned medium stimulation after knockdown of circ-0001649 group（si-circ-0001649+ CM group） and knockdown control with conditioned medium stimulation group（si-NC+CM group）. And the angiogenic and migratory abilities of HUVECs in each group were then detected，as well as the expression of VEGFA and MMP9. After that，inhibition of miR-203a followed by down-regulation of circ-0001649 in HUVECs treated with hAMSC-CM were functional performed to confirm the relative mechanism. Results：The hAMSC-CM significantly increased the angiogenic and migratory capacity of HUVECs，the protein levels of VEGFA and MMP9，and the expression of intracellular circ-0001649. Knockdown of circ-0001649 inhibited the effect of hAMSCs-CM on the angiogenesis and migratory of HUVECs. Bioinformatic analysis and a series of experiments revealed that circ-0001649 could promote the angiogenic and migratory ability of hAMSC-CM on HUVECs by binding miR-203a and then reduced the inhibition of miR-203a on VEGFA and MMP9. Conclusion：The hAMSC-CM up-regulated circ-0001649 in HUVECs，which could binding miR-203a in a ceRNA manner，and promoted angiohenesis by increasing VEGFA and MMP9 expression.
