VEGFA blocking peptide

The "metabolic memory", a phenomenon that the target cell remembers the early hyperglycemia, has been reported to be a critical issue in diabetes pathogenesis. Here, we confirmed the inducible effects of high glucose (HG) and HG followed by normal glucose (HN) upon the proliferation and the tube formation capacity of human umbilical vein endothelial cells (HUVECs), as well as the suppressive effects of HG and HN on HUVEC apoptosis. In the meantime, the miR-320 expression could be dramatically downregulated (** and ## P < 0.01), whereas VEGFA expression (** and ## P < 0.01) and VEGFA, PKC, and RAGE protein levels could be remarkably induced via HG and HN stimulation. More importantly, the effects of HG and HN were not significantly different, suggesting the existence of high glucose-induced metabolic memory and the involvement of miR-320 and VEGFA in high glucose-induced metabolic memory in HUVECs. Consistently, miR-320 overexpression significantly reversed the effects of HG and FIN on HUVECs (* and # P < 0.05, *" and ## P < 0.01). miR-320 suppressed the expression of VEGFA via direct binding to the 3'-UTR of VEGFA mRNA, therefore suppressing high glucose-induced metabolic memory (** P < 0.01); the effects of miR-320 overexpression on HUVECs could be reversed by VEGFA overexpression (# P < 0.05, ## P < 0.01), indicating that miR-320/VEGFA axis modulates the proliferation, apoptosis, and the angiogenesis capacity of HUVECs. In conclusion, we demonstrate that miR-320/VEGFA axis is crucial to high glucose-induced metabolic memory during HUVEC dysfunction and may be involved in the pathology of diabetes.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) implantation shows a repair effect on erectile function in diabetes mellitus-induced erectile dysfunction (DMED) due to its differentiative capacity into endothelial cells (ECs) that contributes to endothelial repair. This study was designed to explore the functional role and mechanism of long noncoding RNA (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in BM-MSCs-mediated DMED repairing. The DMED rat model was established and the erectile function was evaluated by calculating the intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio in the DMED models with or without BM-MSCs implantation. The differentiation of BM-MSCs toward ECs was assessed by measuring the expression of EC-specific genes. RNA pull-down and luciferase reporter assay were performed to explore the interaction between miR-206 and MALAT1 or VEGFA. BM-MSCs implantation improved the erectile function of DMED rats and increased MALAT1 expression. MALAT1 was time-dependently upregulated during the VEGF-induced BM-MSCs differentiation into ECs. Mechanistically, MALAT1 acted as a sponge of miR-206 to upregulate VEGFA expression, thereby promoting the differentiation of BM-MSCs into ECs. Moreover, MALAT1 silencing in vivo impaired the repairing effect of BM-MSCs on erectile dysfunction. Collectively, MALAT1 facilitates BM-MSCs differentiation into ECs via regulating miR-206/VEGFA axis.