MicroRNA-103/107 is involved in hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by targeting HIF-1β

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• 作者：Bi Deng^a ; ^b ; ¹ ; Jie Du^a ; ¹ ; Rong Hu^a ; Ai-Ping Wang^a ; Wei-Hua Wu^c ; Chang-Ping Hu^a ; Yuan-Jian Li^a ; Xiao-Hui Li^a ; ^{xiaohuili@csu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Pulmonary hypertension ; PASMCs ; Proliferation ; miR-103/107 ; HIF-1β
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：147
• 期：Complete
• 页码：117-124
• 全文大小：1225 K

文摘

Activation of hypoxia inducible factor-1 (HIF) is a hallmark in hypoxia-induced pulmonary hypertension (HPH). microRNAs play a significant role in regulating proliferation of pulmonary arterial smooth muscle cells (PASMCs) in pulmonary hypertension. Previous studies have shown that HIF-1β is a target of miR-103/107. In this present study, we aimed to investigate whether miR-103/107 regulate vascular remodeling in HPH via HIF-1β.

Main methods

The HPH model was built by hypoxia exposure in rats. Real-time PCR and Western blotting were used to determine the expression of miR-103/107 and HIF-1β. Proliferation of PASMCs was examined by 5-bromo-2′-deoxyuridine (BrdU) incorporation method. The functions of miR-103/107 on PASMCs proliferation, HIF-1α and HIF-1β expression were assessed by transfecting miR-103/107 mimics and inhibitors.

Key findings

Significant down-regulation of miR-103/107 was observed in remodeled intrapulmonary vascular in HPH rats and hypoxia-exposured PASMCs, whereas HIF-1α and HIF-1β expression were up-regulated. Hypoxia exposure induced significant proliferation of PASMCs, overexpression of miR-103/107 inhibited but miR-103/107 inhibitors exacerbated PASMCs proliferation. Gain-of-function and loss-of-function experiments showed that miR-103/107 expression was inversely correlated with HIF-1β level. No significant changes of HIF-1α expression were observed under miR-103/107 mimic treatment.

Significance

Loss of suppression on HIF-1β by miR-103/107 may contribute to excess proliferation of PASMCs and vascular remodeling in hypoxic pulmonary hypertension.