Extracellular matrix-stimulated phospholipase activation is mediated by beta 1-integrin.
beta 1-Integrins are major mediators of interactions between cells and extracellular matrix (ECM). Adhesion of rat glomerular epithelial cells (GEC) to collagen stimulated phospholipase C. As a result, 1,2-diacylglycerol (DAG) was increased, and inositol phospholipids were decreased in collagen-adherent cells, as compared with GEC adherent to plastic substrata. Adhesion to collagen also stimulated production of free arachidonic acid (the precursor for eicosanoids) due to metabolism of DAG through the DAG lipase pathway and due to phospholipase A2-induced hydrolysis of phospholipids. Phospholipase A2 appeared to be stimulated as a result of protein kinase C (PKC) activation, probably secondary to increased DAG. The collagen-induced increases in DAG and free arachidonic acid, as well as the decrease in inositol phospholipids, were partially inhibited by lowering extracellular Ca2+ concentration to 200 nM or less and by anti-beta 1-integrin antibody Fab. In contrast, anti-beta 1-integrin immunoglobulin G (IgG) enhanced collagen-mediated increases in DAG and arachidonic acid. Proliferation of GEC adherent to collagen was reduced in the presence of anti-beta 1-integrin IgG. The antiproliferative effect of anti-beta 1-IgG appeared to be mediated through PKC, since it was absent in PKC-depleted GEC. Immunoprecipitation with integrin subunit-specific antibodies demonstrated alpha 2 beta 1- and alpha 3 beta 1-integrins in GEC. Thus, in GEC, ECM induces activation of phospholipases C and A2, which is mediated, at least in part, by beta 1-integrins. Products of integrin-mediated phospholipase activation may modulate GEC proliferation.
Cybulsky
A V
AV
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Carbonetto
S
S
Cyr
M D
MD
McTavish
A J
AJ
Huang
Q
Q
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002455:Cell Division; D003094:Collagen / Q000502:physiology; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
C011439:1,2-diacylglycerol; D004075:Diglycerides; D016023:Integrins; D016718:Arachidonic Acid; D003094:Collagen; D010738:Type C Phospholipases; D002118:Calcium