Matrix Metalloproteinase Gelatinase B (MMP-9) Coordinates and Effects Epithelial Regeneration

We studied the role of the matrix metalloproteinase gelatinase B (gelB; MMP-9) in epithelial regeneration using the gelB-deficient mouse. We report the novel finding that, in contrast to other MMPs expressed at the front of the advancing epithelial sheet in wounds of cornea, skin, or trachea, gelB a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-01, Vol.277 (3), p.2065-2072
Main Authors: Mohan, Royce, Chintala, Shravan K., Jung, Jae Chang, Villar, Winston V.L., McCabe, Frank, Russo, Laoti A., Lee, Yunhee, McCarthy, Brendan E., Wollenberg, Kurt R., Jester, James V., Wang, Min, Welgus, Howard G., Shipley, J. Michael, Senior, Robert M., Fini, M. Elizabeth
Format: Article
Language:English
Subjects:
Animals
Basement Membrane
Cornea - cytology
Cornea - enzymology
DNA-Binding Proteins - metabolism
Epithelial Cells - cytology
Epithelial Cells - enzymology
gelB gene
Inflammation - enzymology
Inflammation - pathology
Matrix Metalloproteinase 9 - genetics
Matrix Metalloproteinase 9 - metabolism
Mice
Mice, Knockout
Regeneration
Smad2 Protein
Trans-Activators - metabolism
Wound Healing
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Summary:We studied the role of the matrix metalloproteinase gelatinase B (gelB; MMP-9) in epithelial regeneration using the gelB-deficient mouse. We report the novel finding that, in contrast to other MMPs expressed at the front of the advancing epithelial sheet in wounds of cornea, skin, or trachea, gelB acts to inhibit the rate of wound closure. We determined this to be due to control of cell replication, a novel capacity for MMPs not previously described. We also found that gelB delays the inflammatory response. Acceleration of these processes in gelB-deficient mice is correlated with a delay in signal transduction through Smad2, a transcription factor that inhibits cell proliferation, and in accumulation of epithelial-associated interleukin-1α, a cytokine that inhibits Smad2 signaling and promotes the inflammatory response. GelB-deficient mice also reveal defects in remodeling of extracellular matrix at the epithelial basement membrane zone, in particular, failure to effectively remove the fibrin(ogen) provisional matrix. We conclude that gelB coordinates and effects multiple events involved in the process of epithelial regeneration.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M107611200