Time-resolved proteome profiling of normal lung development

Am J Physiol Lung Cell Mol Physiol. 2018 Jul 1;315(1):L11-L24. doi: 10.1152/ajplung.00316.2017. Epub 2018 Mar 8.

Abstract

Biochemical networks mediating normal lung morphogenesis and function have important implications for ameliorating morbidity and mortality in premature infants. Although several transcript-level studies have examined normal lung development, corresponding protein-level analyses are lacking. Here we performed proteomics analysis of murine lungs from embryonic to early adult ages to identify the molecular networks mediating normal lung development. We identified 8,932 proteins, providing a deep and comprehensive view of the lung proteome. Analysis of the proteomics data revealed discrete modules and the underlying regulatory and signaling network modulating their expression during development. Our data support the cell proliferation that characterizes early lung development and highlight responses of the lung to exposure to a nonsterile oxygen-rich ambient environment and the important role of lipid (surfactant) metabolism in lung development. Comparison of dynamic regulation of proteomic and recent transcriptomic analyses identified biological processes under posttranscriptional control. Our study provides a unique proteomic resource for understanding normal lung formation and function and can be freely accessed at Lungmap.net.

Keywords: computational network analysis; lung development; morphogenesis; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Regulatory Networks / physiology
  • Lung / embryology*
  • Male
  • Mice
  • Proteome / metabolism*
  • Signal Transduction / physiology*
  • Transcriptome / physiology*

Substances

  • Proteome