PPAR-α improves the recovery of lung function following acute respiratory distress syndrome by suppressing the level of TGF-β1

Although peroxisome proliferator-activated receptor (PPAR)-α has been reported to be involved in preventing acute lung injury (ALI), the molecular regulation of post-ALI lung recovery remains to be fully elucidated. The aim of the present study was to characterize the mechanism by which PPAR-α prevents ALI and examine the role of PPAR-α in the recovery of lung function following acute respiratory distress syndrome (ARDS). Reverse transcription-quantitative-polymerase chain reaction and western blot analyses suggested that PPAR-α was effective in suppressing transforming growth factor (TGF)-β1 in HLF cells and RAW 264.7 cells. In an ALI mouse model, PPAR-α treatment prior to stimulation with lipopolysaccharide (LPS) resulted in a decrease in the expression of TGF-β1 in bronchoalveolar lavage fluid (BALF), peripheral blood and splenocytes. The injection of a virus expressing short hairpin PPAR-α into mice following LPS treatment resulted in a dose-dependent increase in lung resistance index and decrease in dynamic compliance, and a significant increase in BALF protein, which indicated PPAR-α was essential for the recovery of lung function following ALI. Of note, the serum expression of PPAR-α was inversely correlated with TGF-β1 and negatively correlated with disease severity in patients with ARDS. These data suggested that PPAR-α was essential for the recovery of lung function following ALI by the suppression of TGF-β1, which reveals a previously unappreciated mechanism controlling post-ALI lung recovery.