Combination of pioglitazone, a PPARγ agonist, and synthetic surfactant B-YL prevents hyperoxia-induced lung injury in adult mice lung explants

Details

• Alternative Title:
  Pulm Pharmacol Ther
• Personal Author:
  Kurihara, Chie ; Sakurai, Reiko ; Chuang, Tsai-Der ; Waring, Alan J. ; Walther, Frans J. ; Rehan, Virender K.
• Description:
  Introduction:
  
  Hyperoxia-induced lung injury is characterized by acute alveolar injury, disrupted epithelial-mesenchymal signaling, oxidative stress, and surfactant dysfunction, yet currently, there is no effective treatment. Although a combination of aerosolized pioglitazone (PGZ) and a synthetic lung surfactant (B-YL peptide, a surfactant protein B mimic) prevents hyperoxia-induced neonatal rat lung injury, whether it is also effective in preventing hyperoxia-induced adult lung injury is unknown.
  
  Method:
  
  Using adult mice lung explants, we characterize the effects of 24 and 72-h (h) exposure to hyperoxia on 1) perturbations in Wingless/Int (Wnt) and Transforming Growth Factor (TGF)-β signaling pathways, which are critical mediators of lung injury, 2) aberrations of lung homeostasis and injury repair pathways, and 3) whether these hyperoxia-induced aberrations can be blocked by concomitant treatment with PGZ and B-YL combination.
  
  Results:
  
  Our study reveals that hyperoxia exposure to adult mouse lung explants causes activation of Wnt (upregulation of key Wnt signaling intermediates β-catenin and LEF-1) and TGF-β (upregulation of key TGF-β signaling intermediates TGF-β type I receptor (ALK5) and SMAD 3) signaling pathways accompanied by an upregulation of myogenic proteins (calponin and fibronectin) and inflammatory cytokines (IL-6, IL-1β, and TNFα), and alterations in key endothelial (VEGF-A and its receptor FLT-1, and PECAM-1) markers. All of these changes were largely mitigated by the PGZ + B-YL combination.
  
  Conclusion:
  
  The effectiveness of the PGZ + B-YL combination in blocking hyperoxia-induced adult mice lung injury ex-vivo is promising to be an effective therapeutic approach for adult lung injury in vivo.
  
  
• Subjects:
  Animals Hyperoxia Lung Lung Injury Mice Pioglitazone PPAR-gamma Agonists PPAR Gamma Surface-Active Agents Transforming Growth Factor Beta
• Keywords:
  Lung Injury PPARγ Surfactant
• Source:
  Pulm Pharmacol Ther. 80:102209
• Pubmed ID:
  36907545
• Pubmed Central ID:
  PMC10205668
• Document Type:
  Journal Article
• Funding:
  K01 IP000050/IP/NCIRD CDC HHSUnited States/ ; R01 HL151769/HL/NHLBI NIH HHSUnited States/
• Volume:
  80
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:28b31e9b7eb14c4c608f3db748ca66907b1ad73059bbe0f035e912d0fb8783063dee60c6bc0a909cbe74d49116e4174a0555d0b3be3a6f4cd33b87ce82ef64cf
• Download URL:
  https://stacks.cdc.gov/view/cdc/157919/cdc_157919_DS1.pdf
• File Type:
  [PDF - 1.36 MB ]