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The density of extracellular matrix proteins regulates inflammation and insulin signaling in adipocytes
Authors:Qinkai Li  Akiko Hata  Nananko Kataoka
Institution:a Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan
b Department of Physiology, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA
Abstract:Cells can not only sense the type of extracellular matrix (ECM) protein that is present in the microenvironment, but they can also sense its density. Here, we investigated the effects of ECM protein density on adipokine secretion and insulin signaling in adipocytes. To this end, 3T3-L1 adipocytes were cultured on the surface of polyacrylamide gels that were coated with gradient densities of a collagen type I and fibronectin mixture. We found that high density ECM causes a decrease in insulin signaling and adiponectin secretion, whereas the secretion of monocyte chemoattractant protein-1 (MCP-1) was increased via the activation of nuclear factor-κB (NF-κB). These results indicate that the density of the ECM directly regulates the inflammatory response and insulin sensitivity of adipocytes.

Structured summary

MINT-7992217: Irs1 (uniprotkb:P35569) physically interacts (MI:0915) with phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha (uniprotkb:P26450) by anti bait coimmunoprecipitation (MI:0006)
Keywords:ECM  extracellular matrix  NF-κB  nuclear factor-κB  MCP-1  monocyte chemoattractant protein-1  IRβ  β subunit of insulin receptor  IRS-1  insulin receptor substrate-1  p85-PI3K  p85 subunit of phosphatidylinositol-3-kinase  SDS-PAGE  sodium dodecyl sulfate-polyacrylamide gel electrophoresis  ECL  enhanced chemiluminescence  BCA  bicinchoninic acid  TGF-β1  transforming growth factor-β1  PAI-1  plasminogen activator inhibitor-1  HMW  high molecular weight  MMW  medium molecular weight  GLUT4  glucose transporter type 4  CS  Calf serum  FBS  fetal bovine serum  IBMX  3-isobutyl-1-methylxanthine  TEMED  N  N  N&prime    N&prime  -tetramethylethylenediamine  PBS  phosphate-buffered saline  FAK  focal adhesion kinase  ERK  extracellular signal-regulated kinase
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