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首页> 外文期刊>Pulmonary pharmacology & therapeutics >Penehyclidine effects the angiogenic potential of pulmonary microvascular endothelial cells
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Penehyclidine effects the angiogenic potential of pulmonary microvascular endothelial cells

机译：戊哒萘胺影响肺部微血管内皮细胞的血管生成潜力

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The present study sought to determine the pharmacological effects of penehyclidine, an anticholinergic agent, on the angiogenic capacity of pulmonary microvascular endothelial cells (PMVECs). In vitro Matrigel network formation assay, cell proliferation assay, cell-matrix adhesion assay, and wound-healing assay were performed in PMVECs with or without exposure to penehyclidine or, in some cases, glycopyrrolate or acetylcholine, over a concentration range. In addition, the phosphorylation state of Akt and ERK, as well as the endogenous level of mTOR and RICTOR were examined in PMVECs by Western blot following the cells exposure to penehyclidine or, for some proteins, glycopyrrolate or acetylcholine. Finally, Western blot for Akt phosphorylation and in vitro Matrigel network formation assay were performed in PMVECs following their exposure to penehyclidine with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or mTOR inhibitor torin-1. We found that, in PMVECs, penehyclidine affected the network formation and cell migration, but not proliferation or cell-matrix adhesion, in a concentration-specific manner, i.e., penehyclidine increased the network formation and cell migration at lower concentrations but increased these processes at higher concentrations. Coincidentally, we observed that penehyclidine concentration-specifically affected the phosphorylation state of Akt in PMVECs, ie., increased Akt phosphorylation at lower concentrations and decreased it at higher concentrations. In contrast, glycopyrrolate was found straightly to decrease network formation and Akt phosphorylation in a concentration dependent manner. Further, we demonstrated that PI3K or mTOR blockade abolished both the enhanced network formation and the increased Akt phosphorylation by penehyclidine. Hence, penehyclidine may differentially alter the angiogenic capacity of PMVECs through affecting the Akt signaling pathway downstream of PI3K and mTOR. Findings from this study suggest a unique pharmacological feature of penehyclidine, which may imply its clinical and therapeutic value in modulating angiogenesis.
机译：本研究试图确定戊甲酸酯，抗胆碱能药物对肺部微血管内皮细胞（PMVEC）的血管生成能力的药理作用。体外Matrigel网络形成测定，细胞增殖测定，细胞 - 基质粘附测定和伤口愈合测定和伤口愈合测定在PMVEC中进行或不接触到戊甲霉素，或在一些情况下，在浓度范围内，甘丙烯酸甲酸酯或乙酰胆碱进行。另外，通过蛋白质印迹在细胞暴露于戊甲霉菌素或对一些蛋白质，甘油吡咯烷酯或乙酰胆碱中，通过Western印迹检查AKT和ERK的磷酸化状态以及MTOR和RUCTOR的内源水平。最后，在其暴露于戊酰胺与磷酸亚氨苄酯3-激酶（PI3K）抑制剂Ly294002或MTOR抑制剂TORIN-1之后，在PMVEC中进行蛋白质印迹和体外Matrigel网络形成测定。我们发现，在PMVECS，戊甲酰胆碱影响网络形成和细胞迁移，但不具有浓度特异性方式的细胞迁移，而不是增殖或细胞 - 基质粘附，即，戊甲霉素在较低浓度下增加网络形成和细胞迁移，但在较低浓度下增加这些过程更高的浓度。巧合地，我们观察到戊甲酸酯浓度 - 特别影响PMVECS中AKT的磷酸化状态，即。，在较低浓度下增加Akt磷酸化并以较高浓度降低。相反，直接发现甘吡咯酸盐以以浓度依赖性方式降低网络形成和Akt磷酸化。此外，我们证明了PI3K或MTOR阻止增强的网络形成和Penehyclidine的增加的AKT磷酸化。因此，戊甲酸酯可以差异地改变PMVECS的血管生成能力，通过影响PI3K和MTOR下游的AKT信号传导途径。本研究的结果表明了戊甲霉素的独特药理学特征，这可能意味着其在调节血管生成中的临床和治疗价值。

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