title: MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1.
abstract: Unbalanced apoptosis is a major cause of structural remodelling of vasculatures associated with PAH (pulmonary arterial hypertension), whereas the underlying mechanisms are still elusive. miRNAs (microRNAs) regulate the expression of several proteins that are important for cell fate, including differentiation, proliferation and apoptosis. It is possible that these regulatory RNA molecules play a role in the development of PAH. To test this hypothesis, we studied the effect of several miRNAs on the apoptosis of cultured PASMCs (pulmonary artery smooth muscle cells) and identified miR-138 to be an important player. miR-138 was expressed in PASMCs, and its expression was subjected to regulation by hypoxia. Expression of exogenous miR-138 suppressed PASMC apoptosis, prevented caspase activation and disrupted Bcl-2 signalling. The serine/threonine kinase Mst1, an amplifier of cell apoptosis, seemed to be a target of miR-138, and the activation of the Akt pathway was necessary for the anti-apoptotic effect of miR-138. Therefore the results of the present study suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and plays an important role in HPVR (hypoxic pulmonary vascular remodelling).
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang 163319, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Ran
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D056151:Airway Remodeling / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D015687:Cell Hypoxia / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics; D000099317:Hippo Kinases
chemical_list: D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C581260:MIRN138 microRNA, rat; C511957:Stk4 protein, rat; D000099317:Hippo Kinases