title: Down-regulation of miR-133a contributes to up-regulation of Rhoa in bronchial smooth muscle cells.
abstract: BACKGROUND
  Augmented bronchial smooth muscle (BSM) contraction is one of the causes of bronchial hyperresponsiveness. The protein RhoA and its downstream pathways have now been proposed as a new target for asthma therapy. MicroRNAs (miRNAs) play important roles in normal and diseased cell functions, and a contribution of miR-133 to RhoA expression has been suggested in cardiomyocytes.
  
  
  OBJECTIVE
  To make clear the mechanism(s) of up-regulation of RhoA observed in the BSMs of experimental asthma, the role of miR-133a in RhoA expression was tested.
  
  
  METHODS
  Total proteins and RNAs (containing miRNAs) were extracted from cultured human BSM cells (hBSMCs) that were treated with antagomirs and/or IL-13, and bronchial tissues of BALB/c mice that were sensitized and repeatedly challenged with ovalbumin. RhoA protein and miR-133a were detected by immunoblotting and quantified real-time reverse transcriptase-polymerase chain reaction, respectively.
  
  
  RESULTS
  In hBSMCs, an up-regulation of RhoA was observed when the function of endogenous miR-133a was inhibited by its antagomir. Treatment of hBSMCs with IL-13 caused an up-regulation of RhoA and a down-regulation of miR-133a. In bronchial tissues of the repeatedly ovalbumin-challenged mice, a significant increase in RhoA was observed. Interestingly, the level of miR-133a was significantly decreased in BSMs of the challenged mice.
  
  
  CONCLUSIONS
  These findings suggest that RhoA expression is negatively regulated by miR-133a in BSMs. IL-13 might, at least in part, contribute to the reduction of miR-133a.
authors: Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. chiba@hoshi.ac.jp
authors: Yoshihiko
authors: Y
authors: Chiba
authors: Miki
authors: M
authors: Tanabe
authors: Kumiko
authors: K
authors: Goto
authors: Hiroyasu
authors: H
authors: Sakai
authors: Miwa
authors: M
authors: Misawa
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D020742:rhoA GTP-Binding Protein