title: Hypoxia inducible factor-1 mediates expression of miR-322: potential role in proliferation and migration of pulmonary arterial smooth muscle cells.
abstract: There is growing evidence that microRNAs play important roles in cellular responses to hypoxia and in pulmonary hypertensive vascular remodeling, but the exact molecular mechanisms involved are not fully elucidated. In this study, we identified miR-322 as one of the microRNAs induced in lungs of chronically hypoxic mice and rats. The expression of miR-322 was also upregulated in primary cultured rat pulmonary arterial smooth muscle cells (PASMC) in response to hypoxia. We demonstrated that HIF-1α, but not HIF-2α, transcriptionally upregulates the expression of miR-322 in hypoxia. Furthermore, miR-322 facilitated the accumulation of HIF-1α in the nucleus and promoted hypoxia-induced cell proliferation and migration. Direct targeting BMPR1a and smad5 by miR-322 was demonstrated in PASMCs suggesting that downregulation of BMP-Smad signaling pathway may be mediating the hypoxia-induced PASMC proliferation and migration. Our study implicates miR-322 in the hypoxic proliferative response of PASMCs suggesting that it may be playing a role in pulmonary vascular remodeling associated with pulmonary hypertension.
authors.affiliation: 1] Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China [2] Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Cardiovascular Surgery, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, Guangdong, 518000, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Chest Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hui
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.
authors.forename: Wenda
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Ramchandran
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
authors.forename: J Usha
authors.initials: JU
authors.lastname: Raj
authors.affiliation: 1] Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen Key Laboratory of Marine Bioresourse and Eco-environmental Science, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong, 518060, China [2] Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
authors.forename: Deming
authors.initials: D
authors.lastname: Gou
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs