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首页> 外文期刊>Pulmonary Circulation >Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension
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Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension

机译：内皮血小板衍生的生长因子介导的肺动脉高压下平滑肌血小板衍生生长因子受体的活化

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Platelet-derived growth factor is one of the major growth factors found in human and mammalian serum and tissues. Abnormal activation of platelet-derived growth factor signaling pathway through platelet-derived growth factor receptors may contribute to the development and progression of pulmonary vascular remodeling and obliterative vascular lesions in patients with pulmonary arterial hypertension. In this study, we examined the expression of platelet-derived growth factor receptor isoforms in pulmonary arterial smooth muscle and pulmonary arterial endothelial cells and investigated whether platelet-derived growth factor secreted from pulmonary arterial smooth muscle cell or pulmonary arterial endothelial cell promotes pulmonary arterial smooth muscle cell proliferation. Our results showed that the protein expression of platelet-derived growth factor receptor a and platelet-derived growth factor receptor b in pulmonary arterial smooth muscle cell was upregulated in patients with idiopathic pulmonary arterial hypertension compared to normal subjects. Platelet-derived growth factor activated platelet-derived growth factor receptor a and platelet-derived growth factor receptor b in pulmonary arterial smooth muscle cell, as determined by phosphorylation of plateletderived growth factor receptor a and platelet-derived growth factor receptor b. The platelet-derived growth factor-mediated activation of platelet-derived growth factor receptor a/platelet-derived growth factor receptor b was enhanced in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal cells. Expression level of plateletderived growth factor-AA and platelet-derived growth factor-BB was greater in the conditioned media collected from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell than from normal pulmonary arterial endothelial cell. Furthermore, incubation of idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell with conditioned culture media from normal pulmonary arterial endothelial cell induced more platelet-derived growth factor receptor a activation than in normal pulmonary arterial smooth muscle cell. Accordingly, the conditioned media from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell resulted in more pulmonary arterial smooth muscle cell proliferation than the media from normal pulmonary arterial endothelial cell. These data indicate that (a) the expression and activity of platelet-derived growth factor receptor are increased in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal pulmonary arterial smooth muscle cell, and (b) pulmonary arterial endothelial cell from idiopathic pulmonary arterial hypertension patients secretes higher level of platelet-derived growth factor than pulmonary arterial endothelial cell from normal subjects. The enhanced secretion (and production) of platelet-derived growth factor from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell and upregulated platelet-derived growth factor receptor expression (and function) in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell may contribute to enhancing plateletderived growth factor/platelet-derived growth factor receptor-associated pulmonary vascular remodeling in pulmonary arterial hypertension.
机译：血小板衍生的生长因子是人和哺乳动物血清和组织中的主要生长因子之一。血小板衍生的生长因子信号通路的异常激活通过血小板衍生的生长因子受体可能有助于肺动脉高压患者肺血管重塑和灭错血管病变的发育和进展。在这项研究中，我们研究了肺动脉平滑肌和肺动脉内皮细胞中血小板衍生的生长因子受体同种型的表达，并研究了肺动脉平滑肌细胞或肺动脉内皮细胞分泌的血小板衍生的生长因子是否促进肺动脉平滑肌细胞增殖。我们的研究结果表明，与正常受试者相比，特发性肺动脉高压患者患有血小板衍生的生长因子受体A和血小板衍生生长因子受体B中的血小板衍生的生长因子受体B.血小板衍生的生长因子活化血小板衍生的生长因子受体A和血小板衍生的生长因子受体B中的肺动脉平滑肌细胞，如血小板生长因子受体A和血小板衍生的生长因子受体B的磷酸化确定。与正常细胞相比，血小板衍生的生长因子受体A /血小板衍生的生长因子受体B的血小板衍生的生长因子受体A /血小板衍生的生长因子受体B的激活增强。在从特发性肺动脉高压肺动脉内皮细胞收集的条件培养基中，血小板的生长因子-AA和血小板衍生的生长因子-BB的表达水平大于来自正常肺动脉内皮细胞的调节培养基。此外，具有来自正常肺动脉内皮细胞的特发性肺动脉高压 - 肺动脉平滑肌细胞的发作性肺动脉高压肌细胞诱导血小板衍生的生长因子受体比在正常肺动脉平滑肌细胞中的活化。因此，来自特发性肺动脉高血压 - 肺动脉内皮细胞的调节培养基导致来自来自正常肺动脉内皮细胞的培养基更高的肺动脉平滑肌细胞增殖。这些数据表明，与正常肺动脉平滑肌细胞（B）来自特发性的肺动脉平滑肌细胞和（B）肺动脉内皮细胞相比，血小板衍生的生长因子受体的表达和活性增加于特发性肺动脉高血压肺动脉细胞中增加肺动脉高血压患者分泌较高水平的血小板衍生的生长因子，而不是来自正常受试者的肺动脉内皮细胞。来自特发性肺动脉高压 - 肺动脉内皮细胞和上调的血小板衍生生长因子受体表达（和功能）在特发性肺动脉高压肌细胞平滑肌细胞中的增强分泌（和生产）可能有助于增强肺动脉高压血液长生长因子/血小板衍生的生长因子受体相关的肺血管重塑。

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