Summary 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. Objectives  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.

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