Endocrine Abstracts

Matrix metalloproteinases (MMPs) play critical roles in embryonic development, morphogenesis, blastocyst implantation, ovulation, post-partum uterine involution, endometrial cycling, bone remodelling and wound healing, and in diseases such as arthritis, cancer, cardiovascular diseases, tissue ulceration and fibrosis. Currently, twenty-four vertebrate MMPs have been reported. An important feature of the MMPs is that many of these genes are inducible by growth factors, cytokines, physical stress, oncogenic transformation, cell-cell and cell-matrix interactions. Our studies on mouse uterus during peri-implantation period indicated striking changes in expression of MMP-2, MMP-9, MT2-MMP and TIMP-3 mRNAs during days 1-8 of pregnancy, suggesting their involvement in early phase of decidualization through ECM modelling.

The activities of MMPs are regulated by the endogenous inhibitors, TIMPs and α2-macroglobulin. The 3D structure of TIMP-1 and TIMP-3 complex revealed the inhibition mechanism of TIMPs. TIMPs exhibit additional biological activities. TIMP-1 and TIMP-2 have mitogenic activity and anti-apoptotic activity. TIMP-3 exhibits apoptotic activity. Most of those cellular activities are independent of the MMP-inhibitory activity.