Overexpression of histone deacetylase SIRT1 exerts an anti-angiogenic role in diabetic retinopathy via miR-20a elevation and YAP/HIF1 α/VEGFA depletion.

Overexpression of histone deacetylase SIRT1 exerts an anti-angiogenic role in diabetic retinopathy via miR-20a elevation and YAP/HIF1α/VEGFA depletion. Am J Physiol Endocrinol Metab. 2020 Aug 10;: Authors: Pan Q, Gao Z, Zhu C, Peng Z, Song M, Li L Abstract As a basic member of the Class III histone deacetylases, SIRT1 has been implicated in the occurrence and progression of diabetic retinopathy (DR). The current study aimed to investigate the roles of SIRT1/miR-20a/YAP/HIF1α/VEGFA in DR. The expression of SIRT1 was initially determined through RT-qPCR and western blot analysis following the successful establishment of a DR mouse model, followed by detection of SIRT1 catalytic activity. Retinal microvascular endothelial cells (RMECs) were cultured in media supplemented with normal glucose (NG) or high glucose (HG). Thereafter, SIRT1 was either silenced or overexpressed in RMECs, after which EdU staining and Matrigel-based tube formation assay were performed to assess cell proliferation and tube formation. The binding relationship between YAP, HIF1α, and VEGFA was further illustrated using dual-luciferase reporter assay. Pre-retinal neovascular cell number was tallied with the IB4 positive vascular endothelial cells determined by immunofluorescence. SIRT1 was poorly expressed in mice with DR and HG-treated RMECs with low catalytic activity. The proliferation and tube formation capabilities of RMECs were elevated under HG conditions,...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research