DNA methyltransferase 3B deficiency unveils a new pathological mechanism of pulmonary hypertension
Yi Yan, Yangyang He, Xin Jiang, Yong Wang, Jiwang Chen, Junhan Zhao, Jue Ye, Tian‐Yu Lian, Xu Zhang, Rujiao Zhang, Dan Lü, Shanshan Guo, Xi-Qi Xu, Kai Sun, Suqi Li, Lianfeng Zhang, Xue Zhang, Shu-Yang Zhang, Zhi‐Cheng Jing
Abstract
rats exhibited more severe pulmonary vascular remodeling. Consistently, inhibition of DNMT3B promoted proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, overexpressing DNMT3B in PASMCs attenuated PDGF-BB-induced proliferation/migration and ameliorated hypoxia-mediated PH and right ventricular hypertrophy in mice. We also showed that DNMT3B transcriptionally regulated inflammatory pathways. Our results reveal that DNMT3B is a previously undefined mediator in the pathogenesis of PH, which couples epigenetic regulations with vascular remodeling and represents a therapeutic target to tackle PH.