title: miR-185/P2Y6 Axis Inhibits Angiotensin II-Induced Human Aortic Vascular Smooth Muscle Cell Proliferation.
abstract: The abnormal proliferation and apoptosis of human aortic vascular smooth muscle cells (HAVSMCs) play an important role in the pathogenesis of hypertension. Recent study revealed that angiotensin II (Ang II) could elicit HAVSMC dysfunction, to induce or aggravate hypertension. Purinergic receptor P2Y6, an inflammation-inducible G protein-coupled receptor, promoted Ang II-induced hypertension. In the present study, we revealed that Ang II induced HAVSMC proliferation and upregulated P2Y6 protein levels. After knockdown of P2Y6, the promotive effect of Ang II on HAVSMC proliferation was restored. microRNAs (miRNAs) involve in most biological processes. In this study, we scanned out seven candidate miRNAs, which were predicted to contain binding site of P2Y6's 3'-UTR by online tools. Among them, miR-185 was significantly downregulated by Ang II treatment. miR-185 reduced P2Y6 protein levels by direct binding to the 3'UTR of P2Y6. miR-185 overexpression suppressed HAVSMC proliferation; P2Y6 overexpression or Ang II treatment promoted HAVSMC proliferation, and restored the suppressive effect of miR-185 on HAVSMC proliferation. Besides, miR-185/P2Y6 axis also affected pERK1/2 protein levels. Taken together, the present study indicated that miR-185/P2Y6 axis might inhibit Ang II-induced HAVSMC proliferation through miR-185 negatively regulating P2Y6 expression and the downstream ERK pathway; rescuing miR-185 expression to inhibit P2Y6 may represent a therapeutic strategy against HAVSMC dysfunction and hypertension.
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .|2 Department of Cardiovascular, The First Hospital of Hunan University of Chinese Medicine , Changsha, China .
authors.forename: Shunmin
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .
authors.forename: Lujun
authors.initials: L
authors.lastname: Tang
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .
authors.forename: Duomei
authors.initials: D
authors.lastname: Lu
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .
authors.forename: Wulei
authors.initials: W
authors.lastname: Duan
authors.affiliation: 1 The Graduate Institute, Hunan University of Chinese Medicine , Changsha City, China .
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: 2 Department of Cardiovascular, The First Hospital of Hunan University of Chinese Medicine , Changsha, China .
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.affiliation: 3 Department of Cardiovascular, First College of Traditional Chinese Medicine, Hunan University of Chinese Medicine , Changsha, China .|4 Department of Cardiovascular, College of Integrated Traditional Chinese and Western Medicine, Hunan Academy of Chinese Medicine , Changsha, China .
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D014652:Vascular Diseases / Q000235:genetics / Q000473:pathology
chemical_list: C552431:MIRN185 microRNA, human; D035683:MicroRNAs; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D000804:Angiotensin II
keywords: P2Y6; angiotensin II; human aortic vascular smooth muscle cells; hypertension; miR-185; proliferation