Document Detail


Conditional depletion of airway progenitor cells induces peribronchiolar fibrosis.
MedLine Citation:
PMID:  20870756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The respiratory epithelium has a remarkable capacity to respond to acute injury. In contrast, repeated epithelial injury is often associated with abnormal repair, inflammation, and fibrosis. There is increasing evidence that nonciliated epithelial cells play important roles in the repair of the bronchiolar epithelium after acute injury. Cellular processes underlying the repair and remodeling of the lung after chronic epithelial injury are poorly understood.
OBJECTIVES: To identify cell processes mediating epithelial regeneration and remodeling after acute and chronic Clara cell depletion.
METHODS: A transgenic mouse model was generated to conditionally express diphtheria toxin A to ablate Clara cells in the adult lung. Epithelial regeneration and peribronchiolar fibrosis were assessed after acute and chronic Clara cell depletion.
MEASUREMENTS AND MAIN RESULTS: Acute Clara cell ablation caused squamous metaplasia of ciliated cells and induced proliferation of residual progenitor cells. Ciliated cells in the bronchioles and pro-surfactant protein C-expressing cells in the bronchiolar alveolar duct junctions did not proliferate. Epithelial cell proliferation occurred at multiple sites along the airways and was not selectively associated with regions around neuroepithelial bodies. Chronic Clara cell depletion resulted in ineffective repair and caused peribronchiolar fibrosis.
CONCLUSIONS: Colocalization of proliferation and cell type-specific markers demonstrate that Clara cells are critical airway progenitor cells. Continuous depletion of Clara cells resulted in persistent squamous metaplasia, lack of normal reepithelialization, and peribronchiolar fibrosis. Induction of proliferation in subepithelial fibroblasts supports the concept that chronic epithelial depletion caused peribronchiolar fibrosis.
Authors:
Anne-Karina T Perl; Dieter Riethmacher; Jeffrey A Whitsett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-24
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  183     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-17     Completed Date:  2011-04-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  511-21     Citation Subset:  AIM; IM    
Affiliation:
Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Anne.Perl@cchmc.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Bronchi / cytology,  metabolism*,  pathology*
Cells, Cultured
Diphtheria Toxin
Disease Models, Animal
Fibrosis
Lung / cytology,  metabolism,  pathology
Mice
Mice, Transgenic
Respiratory Mucosa / cytology,  metabolism*,  pathology*
Stem Cells / cytology,  metabolism*,  pathology*
Grant Support
ID/Acronym/Agency:
HL 090156/HL/NHLBI NIH HHS; R01 HL095580-04/HL/NHLBI NIH HHS; R01 HL104003/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Diphtheria Toxin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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