Adipose-derived stem cell-derived microvesicle-released miR-210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3

Abstract

ADSC, adipose-derived stem cell; MV, micro vesicle; HUVECs, human umbilical vein endothelial cells; RUNX3, Runtrelatedtranscription factor-3.

Hypoxia-Induced miR-210 Is Necessary for Vascular Regeneration upon Acute Limb Ischemia

“…These findings are in agreement with studies on the pro-angiogenic role of miR-210 observed in vitro [15,[31][32][33], as well as in miR-210 overexpression studies in mouse models of heart [20][21][22][23], limb [26], and brain ischemia [24,25,34]. Also concordant are studies showing that cord blood-derived cells expressing miR-210 display an increased potential in stimulating angiogenesis upon transplantation Taken together, these results indicate that miR-210 plays a pro-angiogenic role in vivo also in the absence of ischemic injury.…”

“…In different experimental settings, miR-210 has been shown to stimulate the secretion of pro-angiogenic factors, such as VEGF and FGF2 [23,25,36,[38][39][40], which may play a role in the vascular regeneration process also in the context of hindlimb ischemia. Finally, it is worth noting that miR-210 can be secreted into exosomes and, in this way, transferred from cell to cell, further complicating the scenario [20,26,41].…”

“…This evidence prompted studies aimed at demonstrating the ability of miR-210 to stimulate angiogenesis in ischemic disease models. Driven by a translational purpose, in these investigations, an overexpression strategy in the ischemic tissue was adopted, showing miR-210 s ability to stimulate angiogenesis in heart [20][21][22][23], brain [24,25] and limb ischemia [26]. However, a combination of gain-and loss-of-function approaches is instrumental in providing a clear picture of miR-210 implication in the pathogenetic mechanisms underpinning the ischemia-induced angiogenic response.…”

Effect of Hypoxia-Induced MicroRNA-210 Expression on Cardiovascular Disease and the Underlying Mechanism

“…Interestingly, miR-210 downregulated the EFNA3 protein but not the mRNA in HUVECs [47]. Further, runt-related transcription factor 3 (RUNX3) was also identified as the direct target of miR-210 in HUVECs [51]. Overexpression of miR-210 downregulated RUNX3 and promoted the proliferation and migration of HUVECs, while overexpression of RUNX3 inhibited these effects.…”

“…VEGF is a topical gene that regulates cell proliferation and migration. It was reportedly upregulated in HUVECs in response to hypoxia [37, 47, 51]. Overexpression of miR-210 significantly upregulated VEGF and promoted the proliferation, migration, and invasiveness of HUVECs [21, 38].…”