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Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix.

Publication ,  Journal Article
Snyder, JC; Zemke, AC; Stripp, BR
Published in: Am J Respir Cell Mol Biol
June 2009

Defective epithelial repair in the setting of chronic lung disease has been suggested to contribute to uncontrolled extracellular matrix (ECM) deposition and development of fibrosis. We sought to directly test this hypothesis through gene expression profiling of total lung RNA isolated from mouse models of selective epithelial cell injury that are associated with either productive or abortive repair. Analysis of gene expression in repairing lungs of naphthalene-exposed mice revealed prominent clusters of up-regulated genes with putative roles in regulation of the extracellular matrix and cellular proliferation. Further analysis of tenascin C (Tnc), a representative matrix protein, in total lung RNA revealed a transient 4.5-fold increase in mRNA abundance 1 day after injury and a return to steady-state levels by Recovery Day 3. Tnc was deposited by the peribronchiolar mesenchyme immediately after injury and was remodeled to basement membrane subtending the bronchiolar epithelium during epithelial repair. Epithelial restitution was accompanied by a decrease in Tnc mRNA and protein expression to steady-state levels. In contrast, abortive repair using a transgenic model allowing ablation of all reparative cells led to a progressive increase in Tnc mRNA within lung tissue and accumulation of its gene product within the subepithelial mesenchyme of both conducting airways and alveoli. These data demonstrate that the ECM is dynamically remodeled in response to selective epithelial cell injury and that this process is activated without resolution in the setting of defective airway epithelial repair.

Duke Scholars

Published In

Am J Respir Cell Mol Biol

DOI

EISSN

1535-4989

Publication Date

June 2009

Volume

40

Issue

6

Start / End Page

633 / 642

Location

United States

Related Subject Headings

  • Respiratory System
  • RNA
  • Oligonucleotide Array Sequence Analysis
  • Naphthalenes
  • Mitosis
  • Mice, Transgenic
  • Mice
  • Male
  • Lung
  • Ganciclovir
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Snyder, J. C., Zemke, A. C., & Stripp, B. R. (2009). Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix. Am J Respir Cell Mol Biol, 40(6), 633–642. https://doi.org/10.1165/rcmb.2008-0334OC
Snyder, Joshua C., Anna C. Zemke, and Barry R. Stripp. “Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix.Am J Respir Cell Mol Biol 40, no. 6 (June 2009): 633–42. https://doi.org/10.1165/rcmb.2008-0334OC.
Snyder JC, Zemke AC, Stripp BR. Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix. Am J Respir Cell Mol Biol. 2009 Jun;40(6):633–42.
Snyder, Joshua C., et al. “Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix.Am J Respir Cell Mol Biol, vol. 40, no. 6, June 2009, pp. 633–42. Pubmed, doi:10.1165/rcmb.2008-0334OC.
Snyder JC, Zemke AC, Stripp BR. Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix. Am J Respir Cell Mol Biol. 2009 Jun;40(6):633–642.

Published In

Am J Respir Cell Mol Biol

DOI

EISSN

1535-4989

Publication Date

June 2009

Volume

40

Issue

6

Start / End Page

633 / 642

Location

United States

Related Subject Headings

  • Respiratory System
  • RNA
  • Oligonucleotide Array Sequence Analysis
  • Naphthalenes
  • Mitosis
  • Mice, Transgenic
  • Mice
  • Male
  • Lung
  • Ganciclovir