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Galectin-3 mediates pulmonary vascular endothelial cell dynamics via TRPC1/4 under acute hypoxia

机译:Galectin-3在急性缺氧下通过TRPC1 / 4介导肺血管内皮细胞动力学

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Galectin-3 (Gal-3) has been implicated in various biological functions, yet little is known about its role in regulating the dynamics of pulmonary vascular endothelial cells. Gal-3 was shown to be increased in hypoxic model rats by sequencing analysis. We exposed pulmonary vessel endothelial cells (PVECs) to hypoxia or Gal-3 stimulation, following which cell apoptosis and autophagy were measured with the relevant methods. The results demonstrated that hypoxia elevated nuclear factor-κB (NF-κB) activity and Gal-3 expression. Gla-3 decreased the expression of Bcl-2, Alix, Beclin-1, Atg5, and LC3A/B. The messenger RNA and protein levels of transient receptor potential channel 1/4 (TRPC1/4) and calpain were reduced after Gal-3 treatment. Gal-3 also activated protein kinase B/glycogen synthase kinase-3 β/mammalian target of rapamycin signaling pathways in PVECs. These results suggest that a hypoxia-mediated increase in Gal-3 promotes apoptosis and inhibits autophagy by inhibiting the TRPC1/4 pathway and activating the protein kinase B/glycogen synthase kinase-3 β/mammalian target of rapamycin signaling pathway in PVECs. Furthermore, these results may provide us with a new direction to explore the pathogenesis of pulmonary artery hypertension.
机译:Galectin-3(Gal-3)参与多种生物学功能,但对其在调节肺血管内皮细胞动力学中的作用知之甚少。测序分析显示,在缺氧模型大鼠中,Gal-3增加。我们将肺血管内皮细胞(PVEC)暴露于缺氧或Gal-3刺激下,然后用相关方法检测细胞凋亡和自噬。结果表明,缺氧可提高核因子-κB(NF-κB)活性和Gal-3表达。Gla-3降低了Bcl-2、Alix、Beclin-1、Atg5和LC3A/B的表达。Gal-3治疗后,瞬时受体电位通道1/4(TRPC1/4)和钙蛋白酶的信使RNA和蛋白质水平降低。Gal-3还激活了PVECs中雷帕霉素信号通路的蛋白激酶B/糖原合成酶激酶-3β/哺乳动物靶点。这些结果表明,缺氧介导的Gal-3增加通过抑制TRPC1/4通路和激活PVECs中雷帕霉素信号通路的蛋白激酶B/糖原合成酶激酶-3β/哺乳动物靶来促进细胞凋亡和抑制自噬。此外,这些结果可能为我们探索肺动脉高压的发病机制提供了一个新的方向。

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