MicroRNA-126 Modulates Palmitate-Induced Migration in HUVECs by Downregulating Myosin Light Chain Kinase via the ERK/MAPK Pathway

Abstract

MicroRNA-126 (miR-126) is an endothelial-specific microRNA that has shown beneficial effects on endothelial dysfunction. However, the underlying molecular mechanism is unclear. The present study evaluated the effects of miR-126 on the cell migration and underlying mechanism in HUVECs treated with palmitate. The present results demonstrated that overexpression of miR-126 was found to decrease cell migration in palmitate-treated HUVECs, with decreased MLCK expression and subsequent decreased phosphorylated MLC level. miR-126 also decreased the phosphorylation of MYPT1 in palmitate-treated HUVECs. In addition, it was demonstrated that miR-126 decreases expression of the NADPH oxidase subunits, p67 and Rac family small GTPase 1 with a subsequent decrease in cell apoptosis. Moreover, the phosphorylation of ERK was reduced by miR-126 in palmitate-induced HUVECs. Taken together, the present study showed that the effect of miR-126 on cell migration and cell apoptosis is mediated through downregulation of MLCK via the ERK/MAPK pathway.

Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling

“…These findings are in agreement with the literature, where modulation of other miRNAs has been shown to improve palmitate-induced EC dysfunction. 53 For example, overexpression of miR-155 has been shown to inhibit palmitate-induced apoptosis and promote EC proliferation through regulation of the Wnt signaling pathway, 47 whereas miR-126 modulated EC migration through the ERK (extracellular signal-regulated kinase)/MAPK signaling axis in the presence of palmitate 49 ; however, our study is distinct from others. First, we identified DNAJB9, a member of the UPR pathway, to be directly targeted by miR-409-3p to exert its downstream effects on regulation of EC angiogenesis.…”

“… 43 , 44 Additionally, miRNAs have been implicated in improving various aspects of palmitate-induced EC dysfunction, such as dampening inflammation, apoptosis, and stimulating EC migration. 45 , 46 , 47 , 48 , 49 Here, we used palmitate, a 16-carbon saturated fatty acid and a common circulating saturated FFA, 50 to dissect the role of miR-409-3p and its targets in EC-driven angiogenic responses. Interestingly, while palmitate increased miR-409-3p expression in ECs ( Figure 1 E), neutralization of miR-409-3p expression in ECs in the presence of palmitate significantly increased EC growth and migration ( Figure 2 ), overcoming palmitate-induced EC dysfunction ( Figure S1 ).…”

MEK1/2 inhibitor inhibits neointima formation by activating miR-126-3p/ C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) axis

“…In the contrary, Wang et al demonstrated that miR-126-3p reduced palmitate-induced ERK1/2 phosphorylation in HUVEC. However, miR-126-3p had no effect on ERK1/2 phosphorylation in HUVEC at the basal level [ 33 ]. Those data suggest that miR-126-3p regulates ERK1/2 phosphorylation depending on the specific stimulus with the cells.…”

EPC-EXs improve astrocyte survival and oxidative stress through different uptaking pathways in diabetic hypoxia condition

“…Among the molecules that EXs carry, miRs show the most important role in regulating cellular function. MicroRNA-126 (miR-126) is an endothelial-specific miR found to be expressed in a broad range of tissues, specifically the vascular system and highly vascularized tissues such as lungs and heart [19]. Like all other miRs, miR-126 also has specific functions in angiogenesis and thus is a prospective target for the regulation of vascular integrity and treating various vascular disorders [20,21].…”