A20 attenuates hypoxia-induced pulmonary arterial hypertension by inhibiting NF- κB activation and pulmonary artery smooth muscle cell proliferation.

A20 attenuates hypoxia-induced pulmonary arterial hypertension by inhibiting NF-κB activation and pulmonary artery smooth muscle cell proliferation. Exp Cell Res. 2020 Mar 28;:111982 Authors: Chen M, Ding Z, Zhang F, Shen H, Zhu L, Yang H, Chen S Abstract PAH is a progressive disease characterized by uncontrolled proliferation of PASMCs. Zinc finger protein A20 is a negative feedback regulatory protein of NF-κB activity. The aim of this study was to evaluate zinc finger protein A20 can alleviate PAH in hypoxia exposed mice. C57BL/6 mice received a tail vein injection of adenovirus-mediated ad-A20 and ad-A20 shRNA were exposed to hypoxia. PASMCs isolated from rat pulmonary arteries were cultured in hypoxia, and were transfection of A20 adenovirus. Pulmonary hemodynamic parameters were measured by right heart catheterization. Pulmonary vascular morphological changes were analyzed by HE and α-SMA staining. The expression changes of A20, NF-κB and its downstream protein were detected. The expression of phospho-p65 was increased with the prolongation of hypoxia time. The expression of A20 in lung tissue of chronic hypoxia group decreased with the prolongation of hypoxia time. Adenovirus-mediated A20 (ad-A20) overexpression significantly attenuated the abnormally increased RVSP, RV/(LV + S) ratio, WT%, WA%, α-SMA and the pulmonary vessel muscularization. Ad-A20 treatment markedly attenuated the degradation of phospho-p65 and inhibit...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research