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Am J Physiol Lung Cell Mol Physiol (June 8, 2007). doi:10.1152/ajplung.00028.2007
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Submitted on January 19, 2007
Accepted on June 4, 2007

Membrane-type 1 Matrix Metalloproteinase Is Necessary for Distal Airway Epithelial Repair and Keratinocyte Growth Factor Receptor Expression after Acute Injury

Jeffrey J Atkinson1, Holly M Toennies1, Kenn Holmbeck2, and Robert M. Senior3*

1 Medicine, Pulmonary Division, Washington University in St. Louis, st. louis, Missouri, United States
2 NIDCR, NIH, Bethesda, Maryland, United States
3 Division of Pulmonary and Critical Care, Washington University School of Medicine, St. Louis, Missouri, United States

* To whom correspondence should be addressed. E-mail: rsenior{at}im.wustl.edu.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a protease produced by airway epithelial cells in various diseases. Since other MMPs are involved in bronchial epithelial repair, we investigated the role of MT1-MMP in naphthalene-induced small airway injury and repair in wild-type (WT) and MT1-MMP deficient (KO) mice. The degree of injury was similar in both strains, but the MT1-MMP KO mice were unable to reconstitute a normal fully differentiated airway epithelium 28 days after injury. MT1-MMP was required for the proliferative response in distal airway epithelial cells resulting in decreased cell density and airway epithelial cell differentiation in MT1-MMP KO mice. Surprisingly, epidermal growth factor (EGF)-mediated signaling was unaltered in MT1-MMP KO mice and therefore unrelated to the proliferative response. However, keratinocyte growth factor receptor (KGFR) expression was significantly upregulated prior to the proliferative response and markedly less evident in the distal airway epithelium of MT1-MMP KO mice. These results indicate MT1-MMP is involved in KGFR expression and epithelial cell proliferation after acute airway injury.




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