Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers.
BACKGROUND
Matrix metalloproteinases (MMPs) contribute to matrix remodelling in venous leg ulcers. Extracellular MMP inducer (EMMPRIN; CD147) has been reported to increase MMP expression, and membrane type 1 MMP (MT1-MMP) has been implicated in the activation of MMPs.


OBJECTIVE
To examine whether and to what degree EMMPRIN, MMP-2, MT1-MMP and membrane type 2 MMP (MT2-MMP) are expressed in venous leg ulcers as well as the association with MMP activity.


METHODS
EMMPRIN, MMP-2, MT1-MMP and MT2-MMP were analysed by zymography and immunohistochemistry in biopsies from healthy skin and lesional tissue from venous leg ulcers.


RESULTS
Zymography provided direct evidence of increased proteolytic activity of MMP-2 in lesional skin in comparison with healthy controls. Immunostaining showed intense expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP in dermal structures of venous leg ulcers, whereas only EMMPRIN and MMP-2 showed elevated expression in perivascular regions. Our findings indicate that venous leg ulcers are characterized by elevated expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP. The immunohistological findings of skin alterations reflect the dynamic process of activation of soluble and membrane-bound MMPs, which may be highly induced by EMMPRIN.


CONCLUSIONS
These data suggest for the first time that membrane-bound MMPs may favour enhanced turnover of the extracellular matrix and support unrestrained MMP activity in venous leg ulcers.
Norgauer
J
J
Department of Dermatology, University Medical Center, Hauptstrasse 7, D-79104 Freiburg, Germany.
Hildenbrand
T
T
Idzko
M
M
Panther
E
E
Bandemir
E
E
Hartmann
M
M
Vanscheidt
W
W
Herouy
Y
Y
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D002908:Chronic Disease; D017364:Collagenases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D053517:Matrix Metalloproteinase 15; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D014647:Varicose Ulcer / Q000201:enzymology / Q000378:metabolism*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; C507098:MMP15 protein, human; D008562:Membrane Glycoproteins; D051926:Basigin; D017364:Collagenases; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2