title: Sox9 activation is essential for the recovery of lung function after acute lung injury.
abstract: OBJECTIVE
  Acute lung injury (ALI) often predisposes acute respiratory distress syndrome (ARDS) in humans, and is featured with neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Although the pathogenesis of ALI is relatively well studied, the knowledge on the molecular regulation of the post-ALI lung recovery are poorly understood.
  
  
  METHODS
  Here, we used a widely applied bleomycin-induced ALI model to study the molecular mechanisms that underlie the post-ALI lung recovery in mice. We analyzed Sox9 expression in mouse lung by RT-qPCR, Western blot and immunohistochemistry. We analyzed miR-101 levels in mouse lung by RT-qPCR. We inhibited Sox9 in mouse lung by expressing either shRNA for Sox9 or miR-101, and analyzed the effects of Sox9 suppression on lung recovery.
  
  
  RESULTS
  We detected a significant increase in Sox9 protein but not mRNA, and a signifcant decrease in miR-101 levels in the mouse lung after ALI. MiR-101 was found to target 3'-UTR of Sox9 mRNA to inhibit its expression. Sox9 inhibition by either shRNA for Sox9 or by miR-101 further impaired the functional recovery of the lung after ALI.
  
  
  CONCLUSIONS
  Our data suggest that Sox9 activation is essential for the recovery of lung function after ALI, which highlights a previously unappreciated mechanism that controls the post-ALI lung recovery.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Min
authors.forename: Ruyuan
authors.initials: R
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Hongping
authors.initials: H
authors.lastname: Qu
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Tang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D002460:Cell Line; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D012129:Respiratory Function Tests; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: C581233:MIRN101 microRNA, mouse; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D001761:Bleomycin