The HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of pulmonary microvascular endothelial cells
Year: 2024
Type: article
Abstract: Abnormal histone modification plays vital role in pulmonary hypertension (PH). This study reports the regulation and role of a histone 3 lysine 9 (H3K9) methyltransferase, SETDB1, in primarily cultured rat pulmonary microvascular endothelial cells (PMVECs). Hypoxia induces significant upregulation of SETDB1 at both mRNA and protein levels, in a HIF2α-dependent manner. The hypoxic upregulation of SETDB1 leads to significant apoptosis, senescence, and endothelial-to-mesenchymal transition in PMVECs. Treatment of a specific inhibitor of histone methyltransferase, Chaetocin, effectively attenuates the disease pathogenesis of PH rat model induced by SU5416/hypoxia.
Authors: Yin Zhou, Kai Yang, Zizhou Zhang, Feng Wei, Lishi Chen, Dongling Luo, Ziyang Yang, Kaixun Zhao, Nanshan Xie, Wenrui Li, Shuxin Liang, Mingmei Xiong, Haiyang Tang, Jian Wang, Caojin Zhang
Institutions: First Affiliated Hospital of Guangzhou Medical University, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou Institute of Respiratory Health, Southern Medical University, South China University of Technology, Guangzhou Medical University, Third Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, University of California San Diego
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404024268