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 t...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 human 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,affecting adipogenesis and the development of obesity.Therefore,the activity of MT1-MMP is strictly regulated by multiple mechanisms,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 function and expression of MT1-MMP,and their pharmacotherapeutic implications.展开更多
基金supported by grants from the Canadian Institutes of Health Research(PS 155994)the Natural Sciences and Engineering Research Council of Canada(RGPIN-2016-06479)the National Natural Science Foundation of China(Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao,NSFC 81929002).
文摘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 human 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,affecting adipogenesis and the development of obesity.Therefore,the activity of MT1-MMP is strictly regulated by multiple mechanisms,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 function and expression of MT1-MMP,and their pharmacotherapeutic implications.
