title: MicroRNA-103/107 is involved in hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by targeting HIF-1β.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Loss of suppression on HIF-1β by miR-103/107 may contribute to excess proliferation of PASMCs and vascular remodeling in hypoxic pulmonary hypertension.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China; The Guangxi Zhuang Autonomous Region People's Hospital, Xining 530021, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, Hunan University of Medical, Huaihua 418000, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China. Electronic address: xiaohuili@csu.edu.cn.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000502:physiology
chemical_list: C497398:ARNT protein, rat; C000602463:MIRN103 microRNA, rat; C579315:MIRN107 microRNA, rat; D035683:MicroRNAs; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
keywords: HIF-1β; PASMCs; Proliferation; Pulmonary hypertension; miR-103/107