title: Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation.
abstract: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressing c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells. In this present study, we aimed to investigate whether there is a negative feedback regulation between microRNA let-7g and LOX-1 in hypoxia-induced proliferation of PASMCs.
  
  
  
  SD Rats were exposed to hypoxia (10% O2, 3 weeks) to induce PH. HE staining was used to evaluate pulmonary artery remodeling. in situ hybridization and immunohistochemistry were performed to assess the expression and distribution of let-7g and LOX-1, respectively. MTS, EDU and flow cytometry were performed to evaluate PASMCs proliferation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess the expression of let-7g, LOX-1, calpain-1,-2,-4, and OCT-1.
  
  
  
  The expression of let-7g was significantly down-regulated in pulmonary arteries of hypoxia-induced PH rats accompanied by pulmonary vascular remodeling, whereas let-7g mimic inhibited hypoxia-induced proliferation of PASMCs and up-regulation of LOX-1 expression. LOX-1 blocking reversed hypoxia-induced down-regulation of let-7g expression. Calpains, protein kinase C and OCT-1 were involved in negative feedback regulation between let-7g and LOX-1.
  
  
  
  Negative feedback regulation between let-7g and LOX-1 mediated hypoxia-induced proliferation of in PASMCs.
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Zhu
authors.affiliation: Jiangxi Center of Medical Device Testing, Nanchang, 330029, China.
authors.forename: You-Wen
authors.initials: YW
authors.lastname: Xiong
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Ai-Zhen
authors.initials: AZ
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Ge
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan, 410078, China. Electronic address: huchangping@yahoo.com.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan, 410078, China. Electronic address: zzhang@csu.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D025461:Feedback, Physiological; D000860:Hypoxia; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*
chemical_list: C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; C495136:OLR1 protein, rat; D051127:Scavenger Receptors, Class E
keywords: Cell proliferation; HPH; LOX-1; Negative feedback; let-7g; microRNA