PDGF and IL-1 induce and activate specific protein kinase C isoforms in mesangial cells.
In vitro and in vivo data suggest a remarkable plasticity in the differentiated phenotype of intrinsic glomerular cells, which after injury express new structures and functions. We have shown that a protein kinase C (PKC) isoform, beta II, is expressed in diseased but not normal glomeruli. Since intrarenal cytokine synthesis has been implicated in the pathogenesis of progressive glomerular injury, we have hypothesized that these mediators induce a change in isoform profile. To test this hypothesis in vitro, we have determined whether platelet-derived growth factor (PDGF) and interleukin-1 (IL-1) alter the expression or activation of PKC isoforms in cultured mesangial cells (MCs). By immunoblot and ribonuclease (RNase) protection assays, both PDGF and IL-1 induce as early as 2 h de novo synthesis of PKC-beta II. Since MCs constitutively express PKC-alpha, -beta I, and -zeta, we also determined whether IL-1 or PDGF alter the activity of these isoforms. PDGF maximally induced translocation of PKC-alpha (10 min), -beta I (90 min), -epsilon (120 min), and -zeta (120 min) from the cytosolic to the membrane fraction. IL-1, in contrast, did not alter the distribution of alpha, beta I, or epsilon at any time measured but did induce PKC-zeta translocation. These data suggest inflammatory mediators regulate PKC isoform activity in diseased glomeruli both by de novo synthesis of unexpressed isoforms and by activation of constitutively expressed PKC isoforms.
Ganz
M B
MB
Department of Medicine, Case Western Reserve University, Ohio, USA.
Saksa
B
B
Saxena
R
R
Hawkins
K
K
Sedor
J R
JR
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009693:Nucleic Acid Hybridization; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases
D007375:Interleukin-1; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D012260:Ribonucleases