The P75NTR-induced MicroRNA-30c-2* Impairs Endothelial Cell Survival and Angiogenesis

摘要: MicroRNAs (miRs) negatively regulate the expression of targeted mRNAs. Diabetes induces expression of the anti-angiogenic and pro-apoptotic p75 neurotrophin receptor (p75NTR) in endothelial cells (ECs). Here, we aim to elucidate the contribution of p75NTR-induced miR30c2* in endothelial dysfunction in diabetes. A miR array (Exiqon) was done on human umbilical vein ECs (HUVECs) transduced to overexpress p75NTR (control: Null). miR30c2* expression was further measured by Taqman PCR in HUVECs and CD146+ ECs sorted from the adductor muscles of mice with/out streptozotocin-induced diabetes mellitus. Next, we studied the impact of miR-30c-2* on apoptosis (caspase 3/7 assay) and angiogenesis (Matrigel) in HUVECs cultured under normal conditions or exposed to high D-glucose (HG) and low growth factors (LGF), thus mimicking advanced diabetes, when hyperglycaemia is …