title: MiRNA-30a inhibits AECs-II apoptosis by blocking mitochondrial fission dependent on Drp-1.
abstract: Apoptosis of type II alveolar epithelial cells (AECs-II) is a key determinant of initiation and progression of lung fibrosis. However, the mechanism of miR-30a participation in the regulation of AECs-II apoptosis is ambiguous. In this study, we investigated whether miR-30a could block AECs-II apoptosis by repressing mitochondrial fission dependent on dynamin-related protein-1 (Drp-1). The levels of miR-30a in vivo and in vitro were determined through quantitative real-time PCR (qRT-PCR). The inhibition of miR-30a in AECs-II apoptosis, mitochondrial fission and its dependence on Drp-1, and Drp-1 expression and translocation were detected using miR-30a mimic, inhibitor-transfection method (gain- and loss-of-function), or Drp-1 siRNA technology. Results showed that miR-30a decreased in lung fibrosis. Gain- and loss-of-function studies revealed that the up-regulation of miR-30a could decrease AECs-II apoptosis, inhibit mitochondrial fission, and reduce Drp-1 expression and translocation. MiR-30a mimic/inhibitor and Drp-1 siRNA co-transfection showed that miR-30a could inhibit the mitochondrial fission dependent on Drp-1. This study demonstrated that miR-30a inhibited AECs-II apoptosis by repressing the mitochondrial fission dependent on Drp-1, and could function as a novel therapeutic target for lung fibrosis.
authors.affiliation: Molecular Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Mao
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.forename: Shengcui
authors.initials: S
authors.lastname: Lin
authors.forename: Lili
authors.initials: L
authors.lastname: Jing
authors.forename: Jing
authors.initials: J
authors.lastname: Xiang
authors.forename: Meirong
authors.initials: M
authors.lastname: Wang
authors.forename: Bingsi
authors.initials: B
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.forename: Weili
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Song
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D034281:Dynamins; D004847:Epithelial Cells / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
keywords: AECs-II; Drp-1; apoptosis; lung fibrosis; miRNA-30a; mitochondrial fission