Extracellular matrix remodelling in obesity and metabolic disorders  

作　　者：Vishal Musale David H.Wasserman Li Kang 

机构地区：[1]Division of Systems Medicine,School of Medicine,University of Dundee,Dundee DD19SY,United Kingdom [2]Department of Molecular Physiology and Biophysics,Mouse Metabolic Phenotyping Center,Vanderbilt University,Nashville,TN 37235,United States

出　　处：《Life Metabolism》2023年第4期7-21,共15页生命（代谢（英文）

基　　金：supported by Diabetes UK(15/0005256 and 21/0006329 to L.K.);British Heart Foundation(PG/18/56/33935 to L.K.);European Commission Marie Curie International Incoming Fellowship 625119(to L.K.);National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)(DK059637,DK054902,and DK050277 to D.W.).

摘　　要：Obesity causes extracellular matrix (ECM) remodelling which can develop into serious pathology and fibrosis, having metabolic effects in insulin-sensitive tissues. The ECM components may be increased in response to overnutrition. This review will focus on specific obesity-associated molecular and pathophysiological mechanisms of ECM remodelling and the impact of specific interactions on tissue metabolism. In obesity, a complex network of signalling molecules such as cytokines and growth factors has been implicated in fibrosis. Increased ECM deposition contributes to the pathogenesis of insulin resistance at least in part through the activation of cell surface integrin receptors and CD44 signalling cascades. These cell surface receptors transmit signals to the cell adhesome which orchestrates an intracellular response that adapts to the extracellular environment. Matrix proteins, glycoproteins, and polysaccharides interact through ligand-specific cell surface receptors that interact with the cytosolic adhesion proteins to elicit specific actions. Cell adhesion proteins may have catalytic activity or serve as scaffolds. The vast number of cell surface receptors and the complexity of the cell adhesome have made study of their roles challenging in health and disease. Further complicating the role of ECM-cell receptor interactions is the variation between cell types. This review will focus on recent insights gained from studies of two highly conserved, ubiquitous axes and how they contribute to insulin resistance and metabolic dysfunction in obesity. These are the collagen-integrin receptor-IPP (ILK-PINCH-Parvin) axis and the hyaluronan-CD44 interaction. We speculate that targeting ECM components or their receptor-mediated cell signalling may provide novel insights into the treatment of obesity-associated cardiometabolic complications.

关 键 词：extracellular matrix FIBROSIS insulin resistance OBESITY METABOLISM 

分 类 号：R575.5[医药卫生—消化系统]