Molecular staging of epithelial maturation using secretory cell-specific genes as markers

Am J Respir Cell Mol Biol. 2009 Mar;40(3):340-8. doi: 10.1165/rcmb.2007-0380OC. Epub 2008 Aug 28.

Abstract

Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These changes are poorly described due to a paucity of molecular markers. We used chemical and transgenic approaches to ablate Clara cells, allowing identification of their unique gene expression profile. Flavin monooxygenase 3 (Fmo3), paraoxonase 1 (Pon1), aldehyde oxidase 3 (Aox3), and claudin 10 (Cldn10) were identified as novel Clara cell markers. New and existing Clara cell marker genes were categorized into three classes based on their unique developmental expression pattern. Cldn10 was uniformly expressed in the epithelium at Embryonic Day (E)14.5 and became restricted to secretory cells at E18.5. This transition was defined by induction of CCSP. Maturation of secretory cells was associated with progressive increases in the expression of Fmo3, Pon1, Aox3, and Cyp2f2 between late embryonic and postnatal periods. Messenger RNA abundance of all categories of genes was dramatically decreased after naphthalene-induced airway injury, and displayed a sequence of temporal induction during repair that suggested sequential secretory cell maturation. We have defined a broader repertoire of Clara cell-specific genes that allows staging of epithelial maturation during development and repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Cell Differentiation
  • Claudins
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Epithelium / physiology*
  • Gene Expression Profiling
  • Lung / anatomy & histology
  • Lung / drug effects
  • Lung / embryology
  • Lung / physiology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microarray Analysis
  • Molecular Sequence Data
  • Naphthalenes / pharmacology
  • Respiratory Mucosa / cytology*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / physiology

Substances

  • Biomarkers
  • Claudins
  • Membrane Proteins
  • Naphthalenes
  • claudin 10
  • naphthalene