Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang 163319, China.
Biochem J. 2013 Jun 1;452(2):281-91. doi: 10.1042/BJ20120680.
Unbalanced apoptosis is a major cause of structural remodelling of vasculatures associated with PAH (pulmonary arterial hypertension), whereas the underlying mechanisms are still elusive. miRNAs (microRNAs) regulate the expression of several proteins that are important for cell fate, including differentiation, proliferation and apoptosis. It is possible that these regulatory RNA molecules play a role in the development of PAH. To test this hypothesis, we studied the effect of several miRNAs on the apoptosis of cultured PASMCs (pulmonary artery smooth muscle cells) and identified miR-138 to be an important player. miR-138 was expressed in PASMCs, and its expression was subjected to regulation by hypoxia. Expression of exogenous miR-138 suppressed PASMC apoptosis, prevented caspase activation and disrupted Bcl-2 signalling. The serine/threonine kinase Mst1, an amplifier of cell apoptosis, seemed to be a target of miR-138, and the activation of the Akt pathway was necessary for the anti-apoptotic effect of miR-138. Therefore the results of the present study suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and plays an important role in HPVR (hypoxic pulmonary vascular remodelling).
失衡的细胞凋亡是与肺动脉高压（PAH）相关的脉管系统结构重塑的一个主要原因，而潜在的机制仍难以捉摸。miRNAs（microRNAs）调节着对细胞命运（包括分化、增殖和凋亡）很重要的几种蛋白质的表达。这些调控 RNA 分子可能在 PAH 的发生发展中发挥作用。为了验证这一假说，我们研究了几种 miRNAs 对培养的肺动脉平滑肌细胞（PASMCs）凋亡的影响，并鉴定出 miR-138 是一个重要的调控因子。miR-138 在 PASMCs 中表达，并受缺氧调节。外源性 miR-138 的表达抑制 PASMC 凋亡，阻止半胱天冬酶激活，并破坏 Bcl-2 信号通路。丝氨酸/苏氨酸激酶 Mst1 是细胞凋亡的放大器，似乎是 miR-138 的靶标，而 Akt 通路的激活是 miR-138 抗凋亡作用所必需的。因此，本研究的结果表明，miR-138 似乎是 PASMC 凋亡的负调控因子，在低氧性肺血管重塑（HPVR）中发挥重要作用。
