title: Binding of prorenin to (pro)renin receptor induces the proliferation of human umbilical artery smooth muscle cells via ROS generation and ERK1/2 activation.
abstract: BACKGROUND
  Since the discovery of the (pro)renin receptor (PRR), it has been considered as a novel bioactive molecule of the renin-angiotensin system (RAS). The activation of PRR can elicit a series of angiotensin II (AngII)-independent effects.
  
  
  METHODS
  In this study, we investigated the effects of prorenin and PRR on the proliferation of human umbilical artery smooth muscle (HUASM) cells and explored the possible mechanisms underlying these effects.
  
  
  RESULTS
  The binding of prorenin to PRR can promote proliferation and upregulate the anti-apoptotic protein Bcl-2 and downregulate the pro-apoptotic protein Bax independently of AngII in HUASM cells. In addition, the binding of prorenin to PRR can also increase the production of reactive oxygen species (ROS) and the phosphorylation of extracellular signal-regulated kinase (ERK1/2) independently of AngII. The pretreatment of HUASM cells with an NADPH oxidase inhibitor DPI decreased the production of ROS and also decreased the phosphorylation of ERK1/2. Furthermore, pretreatment of HUASM cells with DPI and the ERK1/2 inhibitor PD98059 significantly attenuated the prorenin-induced proliferation and regulation of apoptosis factors.
  
  
  CONCLUSIONS
  Binding of prorenin to PRR can induce HUASM cell proliferation via the ROS generation and ERK1/2 activation.
authors.affiliation: Dalian Medical University, Dalian, PR China.
authors.forename: Feng Y
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Dalian Medical University, Dalian, PR China.
authors.forename: Xiao Y
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Dalian Medical University, Dalian, PR China.
authors.forename: Li J
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
authors.forename: Yun P
authors.initials: YP
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China yinongjiang@126.com.
authors.forename: Yi N
authors.initials: YN
authors.lastname: Jiang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D000093342:Prorenin Receptor
chemical_list: D000804:Angiotensin II; D019255:NADPH Oxidases; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D051028:bcl-2-Associated X Protein; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor
keywords: (pro)renin receptor; ROS; apoptosis; atherosclerosis; proliferation