Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells
Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells
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通过腺病毒转移 PTEN 基因抑制 Akt1 磷酸化可抑制缺氧诱导的大鼠肺动脉平滑肌细胞增殖
DOI：
10.1016/j.bbrc.2010.05.140
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发表时间：
2010-07-02
影响因子：
3.1
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Luo, Chunxia;Yi, Bin;Feng, Hua
最近的研究发现，肺血管平滑肌细胞(PASMCs)的增殖在肺血管重构中的作用。肌醇磷脂3激酶(PI3K)和丝氨酸/苏氨酸激酶(Akt)蛋白在血管平滑肌细胞中均有表达。此外，10号染色体上缺失的磷酸酶和张力蛋白同源基因(PTEN)被认为是抑制PI3K-Akt通路的细胞因子信号的负调控因子。然而，FTEN/Akt信号在低氧相关血管重构中的作用却知之甚少。在这项研究中，我们发现低氧诱导大鼠PASMCs Akt1mRNA和磷酸化蛋白的表达至少增加了一倍。低氧刺激后，PASMCs胞核中磷酸化PTEN的表达显著减少。用腺病毒介导的PTEN(Ad-PTEN)基因转染法诱导PTEN过表达后，PASMCs中磷酸化Akt1的表达在各时间点均受到显著抑制。此外，我们还发现，低氧使PASMCs的增殖增加近一倍，而PTEN的过度表达显著抑制了低氧诱导的PASMCs的增殖。这些结果提示，低氧条件下PASMCs胞核中磷酸化PTEN的丢失可能是Akt1异常激活的主要原因，因此可能在低氧相关的肺动脉重塑中起重要作用。最后，Ad-PTEN可抑制PASMCs Akt1的磷酸化，提示其对缺氧性肺动脉重塑有潜在的治疗作用。(C)2010 Elsevier Inc.保留所有权利。
Recent findings identify the role of proliferation of pulmonary artery smooth muscle cells (PASMCs) in pulmonary vascular remodeling. Phosphoinositide 3 kinase (PI3K) and serine/threonine kinase (Akt) proteins are expressed in vascular smooth muscle cells. In addition, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been identified as a negative regulator of cytokine signaling that inhibits the PI3K-Akt pathway. However, little is known about the role of FTEN/Akt signaling in hypoxia-associated vascular remodeling. In this study, we found that hypoxia-induced the expression of Akt1 mRNA and phosphorylated protein by at least twofold in rat PASMCs. Phospho-PTEN significantly decreased in the nuclei of PASMCs after hypoxic stimulation. After forcing over-expression of PTEN by adenovirus-mediated PTEN (Ad-PTEN) transfection, the expression of phospho-Akt1 was significantly suppressed in PASMCs at all time-points measured. Additionally, we showed here that hypoxia increased proliferation of PASMCs by nearly twofold and over-expression of PTEN significantly inhibited hypoxia-induced PASMCs proliferation. These findings suggest that phospho-PTEN loss in the nuclei of PASMCs under hypoxic conditions may be the major cause of aberrant activation of Akt1 and may, therefore, play an important role in hypoxia-associated pulmonary arterial remodeling. Finally, the fact that transfection with Ad-PTEN inhibits the phosphorylation of Akt1 in PASMCs suggests a potential therapeutic effect on hypoxia-associated pulmonary arterial remodeling. (C) 2010 Elsevier Inc. All rights reserved.