PMID- 18978301
OWN - NLM
STAT- MEDLINE
DCOM- 20090619
LR  - 20210429
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 40
IP  - 6
DP  - 2009 Jun
TI  - Reparative capacity of airway epithelium impacts deposition and remodeling of 
      extracellular matrix.
PG  - 633-42
LID - 10.1165/rcmb.2008-0334OC [doi]
AB  - 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.
FAU - Snyder, Joshua C
AU  - Snyder JC
AD  - Department of Pulmonary, Allergy and Critical Care Medicine, Duke University 
      Medical Center, Durham, North Carolina 27710, USA.
FAU - Zemke, Anna C
AU  - Zemke AC
FAU - Stripp, Barry R
AU  - Stripp BR
LA  - eng
GR  - F30 ES015960/ES/NIEHS NIH HHS/United States
GR  - ES015960/ES/NIEHS NIH HHS/United States
GR  - HL064888/HL/NHLBI NIH HHS/United States
GR  - HL090146/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081031
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antiviral Agents)
RN  - 0 (Naphthalenes)
RN  - 2166IN72UN (naphthalene)
RN  - 63231-63-0 (RNA)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/pharmacology
MH  - Bronchi/*metabolism
MH  - Epithelial Cells/*metabolism
MH  - Epithelium/metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Ganciclovir/pharmacology
MH  - Lung/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitosis
MH  - Naphthalenes/administration & dosage
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA/metabolism
PMC - PMC2689915
EDAT- 2008/11/04 09:00
MHDA- 2009/06/20 09:00
PMCR- 2010/06/01
CRDT- 2008/11/04 09:00
PHST- 2008/11/04 09:00 [pubmed]
PHST- 2009/06/20 09:00 [medline]
PHST- 2008/11/04 09:00 [entrez]
PHST- 2010/06/01 00:00 [pmc-release]
AID - 2008-0334OC [pii]
AID - ajrcmb406633 [pii]
AID - 10.1165/rcmb.2008-0334OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2009 Jun;40(6):633-42. doi: 10.1165/rcmb.2008-0334OC. 
      Epub 2008 Oct 31.