Increased expression of keratinocyte growth factor represents a stereotypic response to tracheal lumenal insult independent of injury mechanism.
OBJECTIVE
The author hypothesized that keratinocyte growth factor may play a role in mucosal epithelial repair in large conducting airway, and that the nature of the injury, denudation with disruption of the basement membrane by either mechanical or chemical means, versus exfoliation (loss of suprabasal cells only), would be reflected in the growth factor response.


METHODS
This study evaluated the interdependent relationship between respiratory epithelial cells and the surrounding extracellular matrix in response to injury. In human cutaneous models, both keratinocyte growth factor and basic fibroblast growth factor are important in repair process.


METHODS
A sterile tracheal explant culture system was developed that allows for controlled wounding of the epithelial surface using either 1) NaOH, 2) mechanical debridement, or 3) suprabasal exfoliation. Control and injured bovine tracheas were studied by immunohistochemistry up to 24 hours after injury.


RESULTS
Keratinocyte growth factor expression was strongly upregulated in epithelium and submucosa of denuded, but not exfoliation cultures, irrespective of means of injury. Disruption of the basement membrane by any means triggers a stereotypic growth factor response paradigm. This growth factor response has a consistent spatial, but variable, temporal relationship that is influenced by the type of injury-mechanical versus chemical.


CONCLUSIONS
This work demonstrates that the type of injury (denudation vs. exfoliation) affects the expression patterns of growth factors that may be important for airways repair.
Hicks
W L
WL
Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000473:pathology*; D014132:Trachea / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology*
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors