No abstract

BackgroundBronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants, but the mechanisms associated with altered lung development remain poorly understood. Our mouse model of perinatal inflammation mimics the pathophysiology observed in infants with severe BPD. We have previously reported decreased pulmonary miR‐29b expression, and that restoration of miR‐29b expression improves lung development. The current studies tested the hypothesis that decreased expression of miR‐29b was associated with decreases in expression of key protein methyltransferases (PRMTs), and that restoration of miR‐29b would restore expression.MethodsPregnant C3H/HeN mice received an intraperitoneal LPS injection on E16 and newborn pups were exposed in 85% oxygen from birth to 14 days of life. On postnatal day 3, PBS containing a liposomal preparation of miR‐29b or an empty liposome was administered intranasally. On postnatal 28, mouse lung tissues were analyzed for changes in PRMT‐1, PRMT‐5, and symmetrical and asymmetrical dimethylation of histone 4, arginine 3 by western blot.ResultsPerinatal inflammation resulted in decreased expression of PRMT‐1 and PRMT‐5 which led to a decrease in histone 4, arginine 3 symmetrical dimethylation. Liposomal delivery of miR‐29b restored PRMT‐1 and PRMT‐5 expression and partially attenuated the decrease in histone 4 symmetrical methylation.ConclusionOur data suggest that restoration of miR‐29b may prevent aberrant expression of matrix proteins by increasing histone 4, arginine 3 dimethylation and promoting gene silencing.Support or Funding InformationThe authors gratefully acknowledge funding from the NIH/NICHD R01HD0880833This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.