Glomerular mesangial cell adhesion to fibrinogen is mediated by alphavbeta3 integrin.
The biological behavior of glomerular mesangial cells is thought to play a critical role in human and experimental forms of mesangioproliferative glomerulonephritis. In these diseases, mesangial cells proliferate and produce increased amounts of extracellular matrix proteins, which can lead to glomerulosclerosis and end-stage renal disease. Mesangial cells interact with extracellular matrix proteins through integrin-mediated cell adhesion. Fibrinogen as a plasma-derived protein is known to be deposited in the mesangium of kidneys affected by mesangioproliferative glomerulonephritis. The adhesive interactions between fibrinogen and mesangial cells, however, have not been reported. Results in this work show that mesangial cells adhere to immobilized fibrinogen in an integrin-dependent fashion. This process was inhibited by the alphavbeta3-selective peptide cyclo-RGDFV and the monoclonal anti-beta3 integrin chain antibody F11. Ca(2+) ions are a known strong inhibitor of the fibrinogen-alphavbeta3 interaction, and mesangial cell adhesion did not occur when Ca(2+) was the only divalent cation present. Therefore, mesangial cell adhesion to fibrinogen is mediated by alphavbeta3 integrin, and divalent cations have a fundamental role in regulating this process.
Fischer
Edgar G
EG
Department of Pathology, University of New Mexico School of Medicine, Health Sciences Center, BMSB #335, 915 Camino de Salud, Albuquerque, NM 87131, USA. efischer@salud.unm.edu
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology*; D005921:Glomerulonephritis / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D051381:Rats
D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen