Liposomal miR‐29b Delivery Attenuates Increased Expression of Matrix Proteins and Improves Alveolarization in Mice Exposed to Maternal Inflammation and Neonatal Hyperoxia

Abstract

BackgroundChronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants. In addition to decreased alveolarization, these infants can develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Our mouse model mimics the pathophysiology observed in infants with severe BPD and we have previously reported decreased pulmonary miR‐29b expression in this model. The current studies tested the hypothesis that liposomal mediated restoration of miR‐29b in the developing lung will improve lung alveolarization and minimize the pulmonary fibrosis.MethodsMiR‐29 levels were measured in the plasma of preterm infants by PCR. Pregnant 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 day 14 or 28, mouse lung tissues were analyzed for changes in miR‐29 expression, alveolarization, and matrix protein expression.ResultsAnalyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR‐29b levels are suppressed and the levels are inversely correlated to severity in infants later diagnosed with BPD. In our mouse model, modest improvements in alveolarization were detected in the miR‐29b‐treated mice. MiR‐29b treatment completely attenuated the LPS/O2‐associated increases in aSMA, MMP‐9, and SMAD 2/3 and restored PDGFa levels in lung tissues.ConclusionOur data suggest that miR‐29b restoration may represent a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.