Membrane-type Ⅰ matrix metalloproteinase(MT1-MMP),lipid metabolism,and therapeutic implications

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Lipids exert many essential physiological functions,such as serving as a structural component of biological membranes,storing energy,and regulating cell signal transduction.Dysregulation of lipid metabolism can lead to dyslipidemia related to various hu-man diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,lipid metabolism is strictly regulated through multiple mechanisms at different levels,including the extracellular matrix.Membrane-type Ⅰ matrix metalloproteinase(MT1-MMP),a zinc-dependent endopeptidase,proteolytically cleaves extracellular matrix components,and non-matrix proteins,thereby regulating many physiological and pathophysiological processes.Emerging evidence supports the vital role of MT1-MMP in lipid metabolism.For example,MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of atherosclerosis.It also increases the vulnerability of atherosclerotic plaque by promoting collagen cleavage.Furthermore,it can cleave the extracellular matrix of adipocytes,affect-ing adipogenesis and the development of obesity.Therefore,the activity of MT1-MMP is strictly regulated by multiple mecha-nisms,such as autocatalytic cleavage,endocytosis and exocytosis,and post-translational modifications.Here,we summarize the latest advances in MT1-MMP,mainly focusing on its role in lipid metabolism,the molecular mechanisms regulating the func-tion and expression of MT1-MMP,and their pharmacotherapeutic implications.
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