Effect of PI3K/Akt/FoxO1 Signaling Pathway on Apoptosis in Human Pulmonary Artery Smooth Muscle Cell and Pulmonary Hypertension Rat
Objective To investigate the effects of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O1(FoxO1)signaling pathway on apoptosis in human pulmonary artery smooth muscle cell(hPASMC)and pulmonary hypertension rat.Methods In cell experiment section,hPASMC was divided into 4 groups:(1)blank control group;(2)platelet-derived growth factor-BB(PDGF-BB)group;(3)PDGF-BB+LY294002 group;(4)PDGF-BB+paclitaxel group.Cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,the expression levels of Bcl-2,cleaved caspase-3 and PI3 K/Akt/FoxO1 signaling pathway-related proteins were determined using Western blot.In animal experiment section,12 SD rats were randomly divided into 4 groups:(1)blank control group;(2)monocrotaline(MCT)group;(3)MCT+LY294002 group;(4)MCT+paclitaxel group.The expression levels of Bcl-2,cleaved caspase-3 and PI3K/Akt/FoxO1 signaling pathway-related proteins were evaluated using Western blot.Results In the cellular experiments,compared to the PDGF-BB group,the PDGF-BB+LY294002 group and PDGF-BB+paclitaxel group showed the decreased expression levels of Bcl-2(P＜0.01),and the increased expression levels of cleaved caspase-3(P＜0.01).Compared to the blank control group,the PDGF-BB+LY294002 group and PDGF-BB+paclitaxel group showed the increased apoptosis rates(P＜0.01).In the animal experiments,compared to the MCT group,the MCT+LY294002 group and MCT+paclitaxel group showed the decreased expression levels of Bcl-2,phosphorylated Akt and phosphorylated FoxO1(P＜0.01),and the increased expression levels of cleaved caspase-3 and FoxO1(P＜0.01),with no significant difference in PI3K expression levels between the groups.Conclusion The PI3K/Akt/FoxO1 signaling pathway inhibits cell apoptosis in hPASMC and lung tissue of pulmonary hypertension rat.
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