Matrix metalloproteinases: effectors of development and normal physiology

Matrix metalloproteinases: effectors of development and normal physiology

2000 | Thiennu H. Vu and Zena Werb
Matrix metalloproteinases (MMPs) are a family of extracellular proteases that play crucial roles in development and normal physiology. These enzymes are involved in cell migration, invasion, proliferation, and apoptosis, and they regulate various developmental processes such as branching morphogenesis, angiogenesis, wound healing, and extracellular matrix (ECM) degradation. MMPs are activated by the removal of a propeptide and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). The functional roles of MMPs have been elucidated through genetic and pharmacogenetic studies using transgenic mice and chemical inhibitors. MMPs are essential for cell migration by degrading the ECM and altering the microenvironment, influencing cell behavior through the modulation of biologically active molecules, and regulating tissue morphogenesis. In vivo studies have shown that MMPs are involved in implantation, wound healing, mammary development, and bone development. For example, MMP-9 is crucial for trophoblast migration and ECM degradation during implantation, while MMP-3 is important for wound contraction. Targeted inactivation of MMP genes has revealed specific defects in these processes, highlighting the specialized functions of individual MMPs. However, the full extent of MMPs' roles in development remains to be fully elucidated, and further research is needed to identify their relevant in vivo substrates and understand their complex interplay with other cellular processes.Matrix metalloproteinases (MMPs) are a family of extracellular proteases that play crucial roles in development and normal physiology. These enzymes are involved in cell migration, invasion, proliferation, and apoptosis, and they regulate various developmental processes such as branching morphogenesis, angiogenesis, wound healing, and extracellular matrix (ECM) degradation. MMPs are activated by the removal of a propeptide and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). The functional roles of MMPs have been elucidated through genetic and pharmacogenetic studies using transgenic mice and chemical inhibitors. MMPs are essential for cell migration by degrading the ECM and altering the microenvironment, influencing cell behavior through the modulation of biologically active molecules, and regulating tissue morphogenesis. In vivo studies have shown that MMPs are involved in implantation, wound healing, mammary development, and bone development. For example, MMP-9 is crucial for trophoblast migration and ECM degradation during implantation, while MMP-3 is important for wound contraction. Targeted inactivation of MMP genes has revealed specific defects in these processes, highlighting the specialized functions of individual MMPs. However, the full extent of MMPs' roles in development remains to be fully elucidated, and further research is needed to identify their relevant in vivo substrates and understand their complex interplay with other cellular processes.
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Understanding Matrix metalloproteinases%3A effectors of development and normal physiology.