Curcumin Blocks Hyperoxia‐Induced Neonatal Lung Injury by Inhibiting TGFβ Signaling

Objective Our objectives were to determine if curcumin, a potent antioxidant and anti‐inflammatory agent, protects against hyperoxia‐induced neonatal lung injury, and this protection is mediated by blocking TGFβ signaling. Method Fetal day 19 rat lung fibroblasts were exposed to 21% or 95% O 2 for 24h following 1h pretreatment with curcumin. Cell proliferation, differentiation and TGFβ signaling were determined by Western analysis and confocal immunofluoresence. Neonatal rat pups were also exposed to the following conditions: 21% O 2 , 21% O 2 +curcumin (5 mg/kg BW, given i.p. once daily), 95% O 2 , and 95% O 2 +curcumin for 7 days, following which lung injury/repair markers were examined. Results In vitro, curcumin dose‐dependently accelerated e19 fibroblast differentiation and proliferation. Pretreatment with curcumin blocked the hyperoxia‐induced decrease in PPARγ, and increase in αSMA and fibronectin levels. Similarly, in vivo hyperoxia‐induced changes in molecular markers of lung injury/repair [PPARγ, fibronectin, TGFβ ALK5 and Smad3 activation] were blocked by curcumin treatment. Conclusions Curcumin accelerates lung maturation by stimulating key alveolar epithelial‐mesenchymal interactions and it blocks hyperoxia‐induced neonatal lung injury by blocking TGFβ activation, suggesting it as a potential agent against BPD. [Grants support: NIH (HL‐075405, and HD‐051857)].