Bone morphogenetic protein‐7 inhibits endothelial‐mesenchymal transition in pulmonary artery endothelial cell under hypoxia
Bone morphogenetic protein‐7 inhibits endothelial‐mesenchymal transition in pulmonary artery endothelial cell under hypoxia
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DOI：
10.1002/jcp.26195
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发表时间：
2018-05
影响因子：
5.6
通讯作者：
Hongyue Zhang;Y. Liu;Lixin Yan;Wei Du;Xiao-dan Zhang;Min Zhang;He Chen;Yafeng Zhang;
中科院分区：
文献类型：
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作者：
Hongyue Zhang;Y. Liu;Lixin Yan;Wei Du;Xiao-dan Zhang;Min Zhang;He Chen;Yafeng Zhang;
肺动脉高压(PAH)以肺动脉结构改变为特征。在重塑的动脉中几乎普遍发现表达α-平滑肌肌动蛋白(α-SMA)的细胞数量增加。已证实内皮-间质转化(EndoMT)可能是α-SMA表达细胞的来源之一。此外，EndoMT是可逆的。在这里，我们发现，在低氧条件下，骨形态发生蛋白7(BMP-7)的表达在体内和体外都降低了。我们还发现，在常氧条件下，BMP-7缺乏诱导了自发的内源性MT和细胞迁移。经rh-BMP-7处理后，缺氧诱导的内皮细胞内皮细胞m-TOR磷酸化作用明显减弱，BMP-7抑制低氧诱导的肺动脉内皮细胞m-TORC1磷酸化。我们的结果表明，BMP-7通过抑制m-TORC1信号通路来减轻缺氧诱导的EndoMT和细胞迁移。我们的研究揭示了低氧诱导肺动脉内皮细胞内源性MT的新机制，并提出了以EndoMT为靶点治疗肺动脉高压的新策略。
Pulmonary artery hypertension (PAH) is characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing α‐smooth muscle actin (α‐SMA) is a nearly universal finding in the remodeled artery. It has been confirmed endothelial‐to‐mesenchymal transition (EndoMT) may be a source of those α‐SMA–expressing cells. In addition, the EndoMT is reversible. Here, we show that under hypoxia, the expression of bone morphogenetic protein 7 (BMP‐7) was decreased both in vivo and in vitro. We also found that under normoxia, BMP‐7 deficiency induced spontaneous EndoMT and cell migration. The hypoxia‐induced EndoMT and cell migration were markedly attenuated after pretreatment with rh‐BMP‐7. Moreover, m‐TOR phosphorylation was involved in EndoMT and BMP‐7 suppressed hypoxia‐induced m‐TORC1 phosphorylation in pulmonary artery endothelial cells. Our results demonstrate that BMP‐7 attenuates the hypoxia‐induced EndoMT and cell migration by suppressing the m‐TORC1 signaling pathway. Our study revealed a novel mechanism underlying the hypoxia‐induced EndoMT in pulmonary artery endothelial cells and suggested a new therapeutic strategy targeting EndoMT for the treatment of pulmonary arterial hypertension.