piRNA-63076 contributes to pulmonary arterial smooth muscle cell proliferation through acyl-CoA dehydrogenase
piRNA-63076 contributes to pulmonary arterial smooth muscle cell proliferation through acyl-CoA dehydrogenase
复制标题
piRNA-63076 通过酰基辅酶 A 脱氢酶促进肺动脉平滑肌细胞增殖
DOI：
10.1111/jcmm.15179
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发表时间：
2020-03-30
影响因子：
5.3
通讯作者：
Zhu, Daling
中科院分区：
文献类型：
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作者：
Ma, Cui;Zhang, Lixin;Zhu, Daling
Piwi 相互作用 RNA (piRNA) 被认为是种系特异性的，并且参与发育过程中基因组稳定性的维持。最近，已在多种生物体的体细胞中鉴定出 piRNA 表达。然而，piRNA在肺动脉平滑肌细胞（PASMC）增殖中的作用以及缺氧调节肺动脉高压病理过程的分子机制尚不清楚。利用缺氧动物模型、细胞和分子生物学，我们首次获得了piRNA-63076表达在缺氧条件下上调且与细胞增殖呈正相关的证据。随后，我们发现酰基辅酶A脱氢酶（Acadm）受piRNA-63076负向调节并与Piwi蛋白相互作用，参与缺氧PASMC增殖。最后，缺氧条件下 Acadm 的抑制部分归因于 piRNA-63076 介导的 Acadm 启动子区域的 DNA 甲基化。总的来说，这些发现为更好地理解表观遗传学在与 piRNA 相关的肺动脉高压中的作用提供了宝贵的资源。
Piwi-interacting RNAs (piRNAs) are thought to be germline-specific and to be involved in maintaining genome stability during development. Recently, piRNA expression has been identified in somatic cells in diverse organisms. However, the roles of piRNAs in pulmonary arterial smooth muscle cell (PASMC) proliferation and the molecular mechanism underlying the hypoxia-regulated pathological process of pulmonary hypertension are not well understood. Using hypoxic animal models, cell and molecular biology, we obtained the first evidence that the expression of piRNA-63076 was up-regulated in hypoxia and was positively correlated with cell proliferation. Subsequently, we showed that acyl-CoA dehydrogenase (Acadm), which is negatively regulated by piRNA-63076 and interacts with Piwi proteins, was involved in hypoxic PASMC proliferation. Finally, Acadm inhibition under hypoxia was partly attributed to DNA methylation of the Acadm promoter region mediated by piRNA-63076. Overall, these findings represent invaluable resources for better understanding the role of epigenetics in pulmonary hypertension associated with piRNAs.