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

Acta Pharmacologica Sinica
Xiao-Min WeiSheng-Qing Li

Abstract

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.

References

May 1, 1995·American Journal of Respiratory and Critical Care Medicine·M HumbertD Emilie
Oct 27, 1997·Journal of Cellular Physiology·L I RomeroM A Karasek
Jan 18, 2006·Cell Death and Differentiation·N D Perkins, T D Gilmore
Feb 21, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shiou-Hwei YehPei-Jer Chen
Sep 18, 2008·British Journal of Cancer·S PotentaR Kalluri
Nov 7, 2008·Journal of the American Society of Nephrology : JASN·Elisabeth M ZeisbergRaghu Kalluri
Nov 13, 2008·International Journal of Cancer. Journal International Du Cancer·Françoise RévillionGilles Freiss
Sep 22, 2009·American Journal of Respiratory Cell and Molecular Biology·Naozumi HashimotoYoshinori Hasegawa
Jul 9, 2011·The European Respiratory Journal·A M ReynoldsP N Reynolds
Aug 23, 2011·Experimental Eye Research·Jeong Goo LeeEunDuck P Kay
May 5, 2012·Seminars in Cancer Biology·Damian Medici, Raghu Kalluri
Nov 16, 2013·The European Respiratory Journal·Jean-Luc CracowskiMarc Humbert
Mar 14, 2014·Science Translational Medicine·Brian C CooleyManfred Boehm
Aug 27, 2014·The Journal of Clinical Investigation·Elena MagriniUgo Cavallaro
Jan 17, 2015·Circulation·Benoît RanchouxFrédéric Perros
Apr 26, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Seo-Hyun ChoiYoon-Jin Lee
May 10, 2015·The American Journal of Pathology·Robert B GoodAlan M Holmes
Sep 1, 2015·Drug Design, Development and Therapy·X ZhouH Zhou
Nov 1, 2015·The Journal of Clinical Investigation·Pei-Yu ChenMichael Simons
Jan 24, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hao ZhanXiaowu Huang
Jan 29, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sherry E AdesinaRoy L Sutliff
May 5, 2018·American Journal of Respiratory and Critical Care Medicine·Alison BambergDavid W H Riches
Jun 5, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jia-Mei YangJian-Qiang Yu
Nov 14, 2018·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Jie YangYang Gao
Apr 30, 2019·American Journal of Respiratory and Critical Care Medicine·Baktybek KojonazarovRalph Theo Schermuly

❮ Previous
Next ❯

Citations

Mar 28, 2021·Clinical and Experimental Immunology·P Di BenedettoR Giacomelli

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
electrophoresis
immunoprecipitation
RNA-Seq

Software Mentioned

GraphPad Prism
ImageJ

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here