Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1ß/NF-κB/Snail signaling.
Acta Pharmacol Sin
; 41(8): 1102-1110, 2020 Aug.
Article
in En
| MEDLINE
| ID: mdl-32152438
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 1ß (IL-1ß) 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-1ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
NF-kappa B p50 Subunit
/
Interleukin-1beta
/
Protein Tyrosine Phosphatase, Non-Receptor Type 13
/
Cell Transdifferentiation
/
Snail Family Transcription Factors
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Acta Pharmacol Sin
Journal subject:
FARMACOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
China