Published ahead of print on March 1, 2007, doi:10.1165/rcmb.2006-0384OC Am. J. Respir. Cell Mol. Biol., Volume 37, Number 1, July 2007, 48-56 A more recent version of this article appeared on July 1, 2007
Submitted on October 12, 2006 Keratinocyte Growth Factor Improves Repair in the Injured Tracheal EpitheliumBrigitte N Gomperts1*,1 Department of Pediatrics, Mattel Children's Hospital, UCLA, Los Angeles, CA, USA, 2 Department of Medicine, UCLA, Los Angeles, CA, USA, 3 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, USA, 4 University of Virginia School of Medicine, Charlottesville, VA, USA * To whom correspondence should be addressed. E-mail: bgomperts{at}mednet.ucla.edu.
Keratinocyte growth factor (KGF) is a critical growth factor in lung development and is a protective agent after lung injury, although the exact mechanisms of this protective effect have not yet been elucidated. Our laboratory has shown that circulating epithelial progenitor cells can traffic to the airway and they appear to be derived from the bone marrow. On this basis, we hypothesized that KGF and its putative receptor KGFR, would be important to these cells. We showed that the KGF receptor (KGFR), which is found almost exclusively on epithelial cells, was present on cells in the bone marrow and circulation of mice that identified a subpopulation of cytokeratin 5+ circulating epithelial progenitor cells (CEPC). In addition the KGFR co-localized with a population of cytokeratin 5+ basal cells in the repairing proximal airway. Systemic administration of KGF resulted in a significant increase in mobilization of cytokeratin 5+ CEPC at 6 hours post-injection. Administration of KGF to mouse recipients of heterotopic syngeneic tracheal transplants resulted in protection and more rapid repair of the tracheal epithelium with an increase in the number of CEPC in the epithelium of the airway and this effect was abrogated by blocking CEPC with anti-CXCL12 antibodies. KGF therefore appears to be an important growth factor for local resident eprogenitor epithelial cell repair and for mobilization and enhanced engraftment of CEPC to the injured proximal airway epithelium.
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