The aim of the study was to explore the mechanism of mesenchymal stem cell‐derived exosomes (MSC‐EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)‐induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC‐EXO via tail vein injection. Post‐operation, our results showed that MSC‐EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo. In vitro experiment, the hypoxia models of pulmonary artery endothelial cell (PAEC) and pulmonary vascular smooth muscle cell (PASMC) were used. We found that the expression levels of Wnt5a, Wnt11, BMPR2, BMP4 and BMP9 were increased, but β‐catenin, cyclin D1 and TGF‐β1 were decreased in MSC‐EXO group as compared with MCT or hypoxia group in vivo or vitro. However, these increased could be blocked when cells were transfected with Wnt5a siRNA in vitro. Taken together, these results suggested that the mechanism of MSC‐EXO to prevent PH vascular remodelling may be via regulation of Wnt5a/BMP signalling pathway.

中文翻译：

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MSC-EXO通过调节Wnt5a/BMP信号通路对肺动脉高压的保护作用

该研究的目的是探索间充质干细胞衍生的外泌体 (MSC-EXO) 预防实验性肺动脉高压 (PH) 的机制。通过单次腹腔注射 50 mg/kg MCT 成功建立野百合碱 (MCT) 诱导的 PH 大鼠模型，3 周后通过尾静脉注射 MSC-EXO 治疗动物。术后，我们的研究结果表明，MSC-EXO 可以显着降低右心室收缩压 (RVSP) 和右心室肥大指数，减轻体内肺血管重塑和肺纤维化。体外实验采用肺动脉内皮细胞（PAEC）和肺血管平滑肌细胞（PASMC）的缺氧模型。我们发现 Wnt5a、Wnt11、BMPR2、BMP4 和 BMP9 的表达水平升高，但 β-catenin、与体内或体外的 MCT 或缺氧组相比，MSC-EXO 组的 cyclin D1 和 TGF-β1 降低。然而，当在体外用 Wnt5a siRNA 转染细胞时，这些增加可能会被阻止。综上所述，这些结果表明MSC-EXO预防PH血管重构的机制可能是通过调节Wnt5a/BMP信号通路。