Periostin downregulation is an early marker of inhibited neonatal murine lung alveolar septation
The views expressed herein are not necessarily those of the National Institutes of Health.
Supported by, in part, by KL2 RR025760 (S.K.A.; A. Shekhar, PI); as well as Riley Children's Foundation, the Indiana University Department of Pediatrics (Neonatal-Perinatal Medicine) and National Institutes of Health HL115619 (S.J.C.).
Correspondence to: Simon J. Conway or Shawn K. Ahlfeld, 1044 West Walnut Street, Room R4 W402E, Indiana University School of Medicine, Indianapolis, IN 46202. E-mail: firstname.lastname@example.org and email@example.com
Extreme preterm birth exposes the saccular lung to multiple teratogens, which ultimately retard alveolar development. Specifically, therapeutic high level oxygen supplementation adversely affects the premature lungs and results in blunted alveolarization. Prolonged hyperoxic lung injury has previously been shown to upregulate the matricellular protein Periostin (Postn) and stimulate ectopic accumulation of alpha smooth muscle actin (αSMA) myofibroblasts. Therapies that promote lung septation are lacking largely due to a lack of reliable early biomarkers of injury. Thus, we determined if Postn expression correlated with the initial appearance of myofibroblasts in the saccular lung and was required for early alveolar development.
Lung development in C57BL/6J mice following room-air (RA, 21%-O2) or continuous hyperoxia (85%-O2) from birth (P0) through postnatal day P14 was correlated with Postn and αSMA expression. Alveolarization in Postn knockout mice exposed to room-air, 60%-, and 85%-O2 was also examined.
Postn was widely expressed in distal lung septa through P2 to P4 and peak expression coincided with accumulation of saccular myofibroblasts. Initially, 85%-O2 prematurely downregulated Postn and αSMA expression and suppressed proliferation before the first evidence of distal lung simplification at P4. By P14, chronic 85%-O2 resulted in secondary upregulation of Postn and αSMA in blunted septa. Myofibroblast differentiation and alveolar development was unaffected in Postn null mice and acute 85%-O2 exposure equally inhibited septal formation in Postn null and wild-type littermates.
Postn expression is tightly correlated with the presence of αSMA-myofibroblasts and is a novel early biomarker of acutely inhibited alveolar septation during a crucial window of lung development. Birth Defects Research (Part A) 97:373–385, 2013. © 2013 Wiley Periodicals, Inc.