title: miR-100 suppresses mTOR signaling in hypoxia-induced pulmonary hypertension in rats.
abstract: Mammalian Target of Rapamycin (mTOR) is involved in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in human pulmonary hypertension (PH) and animal PH models, and miRNAs are reported to play a key role in modulation of the proliferation of PASMCs. The purposes of this study are to determine the functions of miR-100 and mTOR in cardiovascular remodeling of the hypoxic PH rats and to clarify the correlation between them. We established a rat model of hypoxic PH, which showed an increase in right ventricle systolic pressure, right ventricular and pulmonary vascular remodeling, accompanied by an up-regulation of mTOR and a down-regulation of miR-100. Next, we established an in vitro model of hypoxia-induced proliferation of PASMCs. Consistent with the in vivo findings, hypoxia induced proliferation of PASMCs, accompanied by a down-regulation of miR-100 and an up-regulation of mTOR; these phenomena were reversed by miR-100 mimics or the antagonist of mTOR. Finally, the dual-luciferase reporter gene assay was utilized to reveal the direct interaction between miR-100 and the 3 '-UTR region of mTOR gene. Based on these observations, we conclude that miR-100 can modulate the proliferation of PASMCs in hypoxic PH rats through suppressing the mTOR expression.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Anatomy, School of Medicine, University of South China, Hengyang 421001, China.
authors.forename: Ai-ping
authors.initials: AP
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Pathology, First Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Shao-xin
authors.initials: SX
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Wen-qun
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Chang-ping
authors.initials: CP
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Electronic address: yuan_jianli@sina.com.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: C577629:MIRN100 microRNA, rat; D035683:MicroRNAs; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: MTOR; MiR-100; Proliferation; Pulmonary arterial smooth muscle cells; Pulmonary hypertension; Vascular remodeling