Age-related changes in the cellular composition and epithelial organization of the mouse trachea

PLoS One. 2014 Mar 27;9(3):e93496. doi: 10.1371/journal.pone.0093496. eCollection 2014.

Abstract

We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS) in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggest they arise de novo by budding from the surface epithelium rather than by delayed growth of rudimentary or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the epithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice and an increase in the number of immune cells. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Bronchi / chemistry*
  • Bronchi / metabolism
  • Bronchi / pathology
  • Cell Differentiation
  • Cell Division
  • Cells, Cultured
  • Epithelial Cells / chemistry*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression
  • Keratin-15 / genetics
  • Keratin-15 / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Respiratory Mucosa / chemistry*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Spheroids, Cellular / chemistry*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Trachea / chemistry*
  • Trachea / metabolism
  • Trachea / pathology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Keratin-15
  • Krt15 protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Phosphoproteins
  • Trans-Activators
  • Trp63 protein, mouse

Associated data

  • GEO/GSE55162