Abstract：
Recent evidence suggests that glia maturation factor β (GMFβ) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFβ can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFβ in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFβ is upregulated in the lungs of PAH rats. Knockout GMFβ alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFβ absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFβ reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFβ ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.
摘要：
最近的证据表明，胶质细胞成熟因子β（GMFβ）在肺动脉高压（PAH）的发病机制中很重要。但潜在的机制是未知的。为了阐明GMFβ是否参与肺血管重塑，并探讨IL-6-STAT3通路在此过程中的作用，使用实时定量聚合酶链反应（RT-qPCR）和Westernblot分析检测PAH大鼠中GMFβ的表达，并测量包括骨膜素（POSTN）和白介素6（IL-6）在内的下游分子的表达。还使用免疫荧光在PAH大鼠中测试了POSTN的位置和表达。已证明GMFβ在PAH大鼠肺中上调。敲除GMFβ通过降低右心室收缩压（RVSP）减轻MCT-PAH，平均肺动脉压（mPAP），和肺血管重塑。此外，在缺乏GMFβ的PAH大鼠中，肺血管系统的炎症得到改善。此外,IL-6-STAT3信号通路在PAH中被激活;敲除GMFβ通过抑制IL-6-STAT3信号通路减少POSTN和IL-6的产生。一起来看,这些发现表明敲除GMFβ通过抑制IL-6-STAT3信号通路改善大鼠PAH。
