Periostin downregulation is an early marker of inhibited neonatal murine lung alveolar septation

Shawn K. Ahlfeld, Yong Gao, Jian Wang, Emrin Horgusluoglu, Esther Bolanis, D. Wade Clapp, Simon J. Conway

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)373-385
Number of pages13
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume97
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Alpha smooth muscle actin
  • Bronchopulmonary dysplasia
  • Hyperoxia
  • Myofibroblast
  • Neonatal lung morphogenesis
  • Postn

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

Fingerprint Dive into the research topics of 'Periostin downregulation is an early marker of inhibited neonatal murine lung alveolar septation'. Together they form a unique fingerprint.

  • Cite this