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 interleukin 1β (IL‐1β) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL‐1β or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB 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.

内皮-间质转化（EnMT）在包括肺动脉高压（PH）在内的多种疾病中起着关键作用，而Snail等转录因子是EnMT的关键调节因子。在这项研究中，我们研究了人脐静脉内皮细胞（HUVEC）中的PH危险因素（例如炎症和缺氧）如何调节这些因素。我们发现白介素1β（IL-1β）的治疗通过激活NF-κB/ Snail途径诱导了HUVEC的EnMT，而酪氨酸磷酸酶L1（PTPL1）的敲除进一步加剧了HUVEC的EnMT。我们证明了PTPL1通过去磷酸化和稳定IκBα抑制NF-κB/ Snail。IL-1β或缺氧可能下调HUVEC中的PTPL1表达。PTPL1 /NF-κB信号的去调节在单克他croline诱导的大鼠PH（MCT-PH）模型和临床PH标本中得到验证。