Document Detail

Repair and regeneration of tracheal surface epithelium and submucosal glands in a mouse model of hypoxic-ischemic injury.
MedLine Citation:
PMID:  22617027     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVE: The heterotopic syngeneic tracheal transplant mouse model is an acute hypoxic-ischemic injury model that undergoes complete repair and regeneration. We hypothesized that the repair and regeneration process of the surface epithelium and submucosal glands would occur in a reproducible pattern that could be followed by the expression of specific markers of epithelial cell types.
METHODS: We used the syngeneic heterotopic tracheal transplant model to develop a temporal and spatial map of cellular repair and regeneration by examining the tracheal grafts at post-transplant days 1, 3, 5, 7, 10 and 14. We used pulsed BrdU and immunofluorescent staining to identify and follow proliferating and repairing cell populations.
RESULTS: We confirmed the reproducibility of the injury and repair in the model and we found a distinct sequence of reappearance of the various stem/progenitor and differentiated cell populations of the tracheal surface epithelium and submucosal glands. In the initial phase, the basal and duct cells that survived the injury proliferated to re-epithelialize the basement membrane with K5 and K14 expressing cells. Then these cells proliferated further and differentiated to restore the function of the epithelium. During this repair process, TROP-2 marked all repairing submucosal gland tubules and ducts. Non-CCSP-expressing serous cells were found to differentiate 4-5 days before Clara, mucus and ciliated cells.
CONCLUSIONS: Improving our understanding of the reparative process of the airway epithelium will allow us to identify cell-specific mechanisms of repair that could be used as novel therapeutic approaches for abnormal repair leading to airway diseases.
Ahmed E Hegab; Derek W Nickerson; Vi Luan Ha; Daphne O Darmawan; Brigitte N Gomperts
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Respirology (Carlton, Vic.)     Volume:  17     ISSN:  1440-1843     ISO Abbreviation:  Respirology     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-21     Completed Date:  2013-02-26     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  9616368     Medline TA:  Respirology     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1101-13     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.
Department of Pediatrics, Mattel Children's Hospital, Los Angeles, California, USA.
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MeSH Terms
Anoxia / pathology*
Disease Models, Animal
Fluorescent Antibody Technique
Ischemia / pathology*
Mice, Inbred C57BL
Respiratory Mucosa / pathology,  physiology*
Trachea / blood supply*,  pathology,  physiology*
Grant Support

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