Die Rolle der murinen Matrix-Metalloproteinase-13 in der Embryonalentwicklung und epidermalen Wundheilung

Abstract

Matrix Metalloproteinases are involved in numerous biological processes, which require the remodeling of extracellular matrix including embryogenesis, bone development and remodeling, angiogenesis, metastasis of tumor cells and wound repair of the skin.In the present work the in vivo function of the matrix metalloproteinase 13 (MMP13) was analysed. Both during embryogenesis and in adult mice MMP13 is expressed in bone tissue. In normal skin MMP13 is not expressed, whereas its expression gets strongly induced upon wounding. To analyse the function of MMP13 in embryonic development and cutaneous wound healing, a most recently generated mmp13 knock-out mouse was analysed in detail. MMP-13 deficient mice are viable and show no differences in size and morphology compared to control mice. The loss of MMP13 has no obvious consequence for the bone development. The embryonic development of the skin and its normal homeostasis in adult mice are unchanged in MMP13 deficient mice. Wound healing experiments show a slightly accelerated wound closure in mmp13 knock-out mice compared to control mice. However, the underlying molecular mechanisms remain to be determined. Further important parameters of the process of wound healing, such as the size of granulation tissue, the recruitment of inflammatory cells, angiogenesis, the development of a new collagen matrix and the reconstitution of a new epidermis with an underlying basal membrane are unaffected in the MMP13 mutant mice. These data indicate that MMP13 is not absolutely required for these processes. Alternatively, another MMP compensates the function of MMP13 in these processes. A possible candidate for the compensation is MMP9, which shows a similar expression pattern during the process of wound healing like MMP13. Wound healing experiments with MMP9 deficient mice performed in this work show a somewhat retarded wound closure compared to control mice. This indicates that MMP9 has an accelerating effect on the process of wound healing. The expression of MMP9 at the wound edge of MMP13 deficient mice shown in this work may account for the accelerated wound closure seen in MMP13 deficient mice.