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首页> 外文期刊>American Journal of Physiology >MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration.
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MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration.

机译：MicroRNA-21在缺氧介导的肺动脉平滑肌细胞增殖和迁移中起作用。

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摘要

Hypoxia stimulates pulmonary artery smooth muscle cell (PASMC) proliferation. Recent studies have implicated an important role for microRNAs (miRNAs) in hypoxia-mediated responses in various cellular processes, including cell proliferation. In this study, we investigated the role of microRNA-21 (miR-21) in hypoxia-induced PASMC proliferation and migration. We first demonstrated that miR-21 expression increased by approximately 3-fold in human PASMC after 6 h of hypoxia (3% O) and remained high ( approximately 2-fold) after 24 h of hypoxia. Knockdown of miR-21 with anti-miR-21 inhibitors significantly reduced hypoxia-induced cell proliferation, whereas miR-21 overexpression in normoxia enhanced cell proliferation. We also found that miR-21 is essential for hypoxia-induced cell migration. Protein expression of miR-21 target genes, specifically programmed cell death protein 4 (PDCD4), Sprouty 2 (SPRY2), and peroxisome proliferator-activated receptor-alpha (PPARalpha), was decreased in hypoxia and in PASMC overexpressing miR-21 in normoxia and increased in hypoxic cells in which miR-21 was knocked down. In addition, PPARalpha 3'-untranslated region (UTR) luciferase-based reporter gene assays demonstrated that PPARalpha is a direct target of miR-21. Taken together, our findings indicate that miR-21 plays a significant role in hypoxia-induced pulmonary vascular smooth muscle cell proliferation and migration by regulating multiple gene targets.
机译：低氧刺激肺动脉平滑肌细胞（PASMC）增殖。最近的研究表明，microRNA（miRNA）在多种细胞过程（包括细胞增殖）中的缺氧介导的反应中起着重要作用。在这项研究中，我们调查了microRNA-21（miR-21）在缺氧诱导的PASMC增殖和迁移中的作用。我们首先证明，在缺氧6小时（3％O）后，人PASMC中miR-21表达增加约3倍，在缺氧24小时后仍保持高表达（约2倍）。用抗miR-21抑制剂抑制miR-21可以显着减少缺氧诱导的细胞增殖，而在常氧状态下miR-21的过表达会增强细胞增殖。我们还发现miR-21对于缺氧诱导的细胞迁移至关重要。 miR-21靶基因的蛋白质表达，特别是程序性细胞死亡蛋白4（PDCD4），Sprouty 2（SPRY2）和过氧化物酶体增殖物激活受体-α（PPARalpha），在低氧状态下降低，而在常氧状态下PASMC过表达miR-21并在敲低miR-21的低氧细胞中增加。此外，基于PPARalpha 3'非翻译区（UTR）荧光素酶的报道基因检测表明，PPARalpha是miR-21的直接靶标。综上所述，我们的发现表明，miR-21通过调节多个基因靶点在低氧诱导的肺血管平滑肌细胞增殖和迁移中起重要作用。

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