TY - JOUR
T1 - Membrane type 1 matrix metalloproteinase is necessary for distal airway epithelial repair and keratinocyte growth factor receptor expression after acute injury
AU - Atkinson, Jeffrey J
AU - Toennies, Holly M
AU - Holmbeck, Kenn
AU - Senior, Robert M
PY - 2007/9
Y1 - 2007/9
N2 - 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-knockout (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, 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 before 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.
AB - 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-knockout (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, 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 before 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.
KW - Animals
KW - Cell Count
KW - Cell Proliferation/drug effects
KW - Epidermal Growth Factor/pharmacology
KW - Epithelial Cells/drug effects
KW - Epithelium/enzymology
KW - Gene Expression Regulation, Enzymologic/drug effects
KW - Matrix Metalloproteinase 14/genetics
KW - Mice
KW - Mice, Knockout
KW - Naphthalenes/administration & dosage
KW - RNA, Messenger/genetics
KW - Receptor, Epidermal Growth Factor/metabolism
KW - Receptor, Fibroblast Growth Factor, Type 2/genetics
KW - Respiratory System/drug effects
KW - Signal Transduction/drug effects
KW - Up-Regulation/drug effects
KW - Wound Healing/drug effects
U2 - 10.1152/ajplung.00028.2007
DO - 10.1152/ajplung.00028.2007
M3 - Journal article
C2 - 17557804
SN - 1040-0605
VL - 293
SP - L600-10
JO - American Journal of Physiology: Lung Cellular and Molecular Physiology
JF - American Journal of Physiology: Lung Cellular and Molecular Physiology
IS - 3
ER -