LAUSR

BackgroundP16 methylation plays an important role in the pathogenesis of hyperoxia-induced lung fibrosis. 5-aza-2′-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. In this study, the effects of 5-aza-CdR on a hyperoxia-induced lung fibrosis in neonatal rats were investigated.MethodsRat pups were exposed to 85% O2 for 21 days of and received intraperitoneal injections of 5-aza-CdR or normal saline (NS) once every other day. Survival rates and lung coefficients were calculated. Hematoxylin–eosin staining was performed to analyze the degree of lung fibrosis. Collagen content and TGF-β1 levels were determined. A methylation-specific polymerase chain reaction and western blotting were performed to determine P16 methylation status and P16, cyclin D1, and E2F1 protein expression.Results5-aza-CdR treatment during hyperoxia significantly improved the survival rate and weight gain, while it decreases the degree of lung fibrosis and levels of hydroxyproline and TGF-β1. Hyperoxia induced abnormal P16 methylation and 5-aza-CdR effectively reversed the hypermethylation of P16. Expression of the P16 protein in lung tissues was enhanced, while cyclin D1 and E2F1 protein were reduced by 5-aza-CdR treatment during hyperoxia.ConclusionThese data show that 5-aza-CdR attenuated lung fibrosis in neonatal rats exposed to hyperoxia by lowering hydroxyproline and TGF-β1 expression and via re-expression of P16 in neonatal rats.