血小板源性生长因子受体
缺氧(环境)
转化生长因子
癌症研究
肺动脉
伊马替尼
药理学
内科学
医学
生长因子
受体
化学
氧气
有机化学
髓系白血病
作者
Shasha Song,Min Zhang,Zhi Yi,Hongyue Zhang,Tingting Shen,Xuezhong Yu,Chen Zhang,Xiaodong Zheng,Lei Yu,Cui Ma,Yang Liu,Daling Zhu
标识
DOI:10.1016/j.cellsig.2016.06.022
摘要
Endothelial-to-mesenchymal transition (EndoMT) has been recognized as a major reason for the pulmonary artery remodeling (PAR) in pulmonary artery hypertension (PAH). However, the molecular mechanisms and regulatory pathways involved in the EndoMT remain undefined. In the present study, we have confirmed that EndoMT was occurred in pulmonary arteries of rats induced by hypoxia and monocrotaline and in hypoxic pulmonary artery endothelial cells (PAECs). Moreover, hypoxia increased the expression of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) and decreased the expression of neprilysin (NEP), which contributed to the hypoxia-induced EndoMT of PAECs. Furthermore, a reciprocal regulation of PDGF-B and TGF-β1 induced by decreasing NEP promoted the EndoMT of PAECs under hypoxia, which was a novel molecular mechanism to reveal the EndoMT participating in PAR. More importantly, imatinib, a PDGF receptor antagonist, relieved PAR and EndoMT in PAH rats. Thus, our results identify a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease.
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