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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2018

Open Access 01-12-2018 | Research article

Inhibition of Shp2 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats

Authors: Yusheng Cheng, Min Yu, Jian Xu, Mengyu He, Hong Wang, Hui Kong, Weiping Xie

Published in: BMC Pulmonary Medicine | Issue 1/2018

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Abstract

Background

Src homology 2 containing protein tyrosine phosphatase (PTP) 2 (Shp2) is a typical tyrosine phosphatase interacting with receptor tyrosine kinase to regulate multiple signaling pathways in diverse pathological processes. Here, we will investigate the effect of Shp2 inhibition on pulmonary arterial hypertension (PAH) in a rat model and its potential cellular and molecular mechanisms underlying.

Methods

Monocrotaline (MCT)-induced PAH rat model was used in this study. Phps-1, a highly selective inhibitor for Shp2, was administered from 21 days to 35 days after MCT single-injection. Microcatheter method was applied to detected hemodynamic parameters. Histological methods were used to determine PVR changes in PAH rats. Moreover, cultured pulmonary artery smooth muscle cells (PASMCs) treated by platelet-derived growth factor (PDGF) with or without Phps-1 was used to investigate the potential cellular and molecular mechanisms underlying in vitro.

Results

Inhibition of Shp2 significantly attenuated MCT-induced increases of mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in rats. Shp2 inhibition effectively decreased thickening of pulmonary artery media and cardiomyocyte hypertrophy as well as perivascular and myocardial fibrosis in MCT-treated rats. Moreover, Shp2 inhibition ameliorated muscularization of pulmonary arterioles in MCT-induced PAH rats. Shp2 inhibition significantly reduced platelet-derived growth factor (PDGF)-triggered proliferation and migration of human pulmonary artery smooth muscle cells (PASMCs), which might be attributed to the inactivations of Akt and Stat3 pathways.

Conclusions

Shp2 contributes to the development of PAH in rats, which might be a potential target for the treatment of PAH.
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Metadata
Title
Inhibition of Shp2 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats
Authors
Yusheng Cheng
Min Yu
Jian Xu
Mengyu He
Hong Wang
Hui Kong
Weiping Xie
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-018-0700-y

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