Protein tyrosine phosphatase L1 represses endothelialmesenchymal transition by inhibiting IL-1β/NF-κB/Snail signaling

Authors: Xiao-min Wei1, Gulinuer Wumaier1, Ning Zhu1, Liang Dong1, Cheng-wei Li1, Jing-wen Xia1, You-zhi Zhang1, Peng Zhang1, Xiu-juan Zhang1, Yuan-yuan Zhang1, Sheng-qing Li1
1 Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
Correspondence to: Sheng-qing Li:,
DOI: 10.1038/s41401-020-0374-x
Received: 18 August 2019
Accepted: 4 February 2020
Advance online: 9 March 2020


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.
Keywords: pulmonary hypertension; endothelial–mesenchymal transition (EnMT); NF-κB; protein tyrosine phosphatase L1 (PTPL1); human umbilical vein endothelial cells (HUVECs)

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