ABSTRACT Venous ulcer is a common contributor to chronic venous insufficiency (CVI) of lower limbs, which seriously affects the life quality of patients. In this study, we researched the expression… Click to show full abstract
ABSTRACT Venous ulcer is a common contributor to chronic venous insufficiency (CVI) of lower limbs, which seriously affects the life quality of patients. In this study, we researched the expression characteristics of microRNA-301a-3p (miR-301a-3p) in patients with CVI and investigated the impact of miR-301a-3p on the dysfunction of human umbilical vein endothelial cells (HUVECs). The plasma level of miR-301a-3p in normal controls, patients with varicose great saphenous vein, and patients with the venous ulcer of lower limbs were measured. We adopted Interleukin-1β (IL-1β), H2O2, and oxygen and glucose deprivation (OGD) to induce endothelial cell injury in vitro. In this way, we evaluated the influence of miR-301a-3p on HUVEC viability, apoptosis, inflammatory response, and oxidative stress. Our data showed that miR-301a-3p was substantially overexpressed in patients with lower limb venous ulcers. The viability of HUVECs decreased, and miR-301a-3p was up-regulated after IL-1β, H2O2, and OGD treatment. miR-301a-3p inhibition greatly ameliorated the dysfunction and cell damage of HUVECs, promoted IGF1/PI3K/Akt/PPARγ, and down-regulated NF-κB/MMPs. The phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) or the peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor (GW9661) reversed the anti-inflammatory, antioxidant, and anti-apoptotic effects mediated by miR-301a-3p down-regulation. The nuclear factor-κB (NF-κB) inhibitor lessened cell injury mediated by miR-301a-3p overexpression. In terms of the mechanism, miR-301a-3p targeted the 3ʹUTR of Insulin-like growth factor-1 (IGF1) and repressed the profile of IGF1. Thus, miR-301a-3p mediates venous endothelial cell damage by targeting IGF1 and regulating the IGF1/PI3K/Akt/PPARγ/NF-κB/MMPs pathway. GRAPHICAL ABSTRACT
               
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