Biochemical insights into the role of matrix metalloproteinases in regeneration: challenges and recent developments.
Matrix metalloproteinases (MMPs) are a group of proteases that belong to the metazincin family. These proteins consist of similar structures featuring a signaling peptide, a propeptide domain, a catalytic domain where the notable zinc ion binding site is found and a hinge region that binds to the C-terminal hemoplexin domain. MMPs can be produced by numerous cell types through secretion or localization to the cell membrane. While certain chemical compounds have been known to generally inhibit MMPs, naturally occurring proteins known as tissue inhibitors of metalloproteinases (TIMPs) effectively interact with MMPs to modify their biological roles. MMPs are very important enzymes that actively participate in remodeling the extracellular matrix by degrading certain constituents, along with promoting cell proliferation, migration, differentiation, apoptosis and angiogenesis. In normal adult tissue, they are almost undetectable; however, when perturbed through injury, disease or pregnancy, they have elevated expression. The goal of this review is to identify new experimental findings that have provided further insight into the role of MMPs in skeletal muscle, nerve and dermal tissue, as well as in the liver, heart and kidneys. Increased expression of MMPs can improve the regeneration potential of wounds; however, an imbalance between MMP and TIMP expression can prove to be destructive for afflicted tissues.
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The Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of UPMC, and Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213-2582, USA.
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D000818:Animals; D002490:Central Nervous System / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology; D011247:Pregnancy; D011498:Protein Precursors / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000737:chemistry / Q000378:metabolism
D061965:Matrix Metalloproteinase Inhibitors; D011498:Protein Precursors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases