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

• Published in: Acta pharmacologica Sinica Vol. 41; no. 8; pp. 1102 - 1110
• Main Authors: Wei, Xiao-min, Wumaier, Gulinuer, Zhu, Ning, Dong, Liang, Li, Cheng-wei, Xia, Jing-wen, Zhang, You-zhi, Zhang, Peng, Zhang, Xiu-juan, Zhang, Yuan-yuan, Li, Sheng-qing
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.08.2020; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Biomedicine; Endothelial cells; Hypoxia; IL-1β; Immunology; Internal Medicine; Lung diseases; Medical Microbiology; Mesenchyme; Monocrotaline; NF-κB protein; Pharmacology/Toxicology; Phosphatase; Protein-tyrosine-phosphatase; Risk factors; Snail protein; Therapeutic applications; Transcription factors; Umbilical vein; Vaccine; protein tyrosine phosphatase L1 (PTPL1); NF-κB; endothelial–mesenchymal transition (EnMT); pulmonary hypertension; human umbilical vein endothelial cells (HUVECs)
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/s41401-020-0374-x

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.