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Troglitazone upregulates PTEN expression and induces the apoptosis of pulmonary artery smooth muscle cells under hypoxic conditions.

Abstract：

:The increased proliferation and decreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the main causes of hypoxic pulmonary hypertension. In this study, we investigated the role of troglitazone [peroxisome proliferator-activated receptor γ (PPARγ) agonist] in the regulation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression and the apoptosis of PASMCs under hypoxic conditions. Normal human PASMCs were cultured in growth medium (GM) and treated with troglitazone (0.5-80 µM) under hypoxic conditions (5% CO2+94% N2+1% O2) for 72 h. The gene expression of PTEN, AKT-1 and AKT-2 was determined by quantitative reverse transcription PCR (qRT-PCR). The protein expression level of PTEN, AKT and phosphorylated AKT (p-AKT) was determined by western blot analysis. The apoptosis of PASMCs was determined by measuring the activities of caspase-3, -8 and -9 and by TUNEL assay. The proliferation rate of the PASMCs was altered in a concentration-dependent manner by troglitazone. A significantly reduced proliferation rate was observed at troglitazone concentrations starting from 20 µM under hypoxic conditions (72 ± 5.8%). Although the gene expression levels of PTEN were increased, the gene expression levels of AKT-1 and AKT-2 remained unaltered. Consistent with this, PTEN protein expression was also altered in a concentration-dependent manner by troglitazone. Although AKT expression was unaltered in all the cell samples, reduced p-AKT expression was observed in the troglitazone-treated PASMCs. Troglitazone increased the activities of caspase-3, -8 and -9 in the PASMCs. bpV(HOpic) (PTEN inhibitor) and GW9662 (PPARγ inhibitor) inhibited PTEN protein expression and recovered the proliferation rate of the PASMCs. TUNEL assay demonstrated that troglitazone significantly increased the apoptosis of PASMCs under hypoxic conditions. In conclusion, troglitazone increases PTEN expression under hypoxic conditions in a concentration-dependent manner. Troglitazone increases the apoptosis of PASMCs under hypoxic conditions. The increase in PTEN expression is mediated through the PPARγ signaling pathway.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Pi WF,Guo XJ,Su LP,Xu WG

doi

10.3892/ijmm.2013.1487

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1101-9

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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Troglitazone upregulates PTEN expression and induces the apoptosis of pulmonary artery smooth muscle cells under hypoxic conditions.