,Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1β/NF

• 作 者: Xiao-min Wei Gulinuer Wumaier Ning Zhu Liang Dong Cheng-wei Li Jing-wen Xia You-zhi Zhang Peng Zhang Xiu-juan Zhang Yuan-yuan Zhang Sheng-qing Li
• 机 构: Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai 200
• 出 处: 中国药理学报（英文版）
• 发表日期: 2020年8期
• 关键词: pulmonary hypertension endothelial-mesenchymal transition (EnMT) NF-KB protein t

Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases,including pulmonary hypertension (PH),and transcription factors like Snail are key regulators of EnMT.In this study we investigated how these factors were regulated by PH risk factors (e.g.inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs).We showed that treatment with intedeukin 1β (IL-1β) induced EnMT of HUVECs via activation of NF-KB/Snail pathway,which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1).We demonstrated that PTPL1 inhibited NF-KB/Snail through dephosphorylating and stabilizing IKBα.IL-1β or hypoxia could downregulate PTPL1 expression in HUVECs.The deregulation of PTPL1/NF-KB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens.Our findings provide novel insights into the regulatory mechanisms of EnMT,and have implications for identifying new therapeutic targets for clinical PH.