PDGF and IL-1 induce and activate specific protein kinase C isoforms in mesangial cells

Michael B. Ganz, Brett Saksa, Ramesh Saxena, Karen Hawkins, John R. Sedor

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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, βn, 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-βn. Since MCs constitutively express PKC-a, -βj, and -£, we also determined whether IL-1 or PDGF alter the activity of these isoforms. PDGF maximally induced translocation of PKC-a (10 min), -βi (90 min), -e (120 min), and -£ (120 min) from the cytosolic to the membrane fraction. IL-1, in contrast, did not alter the distribution of a, βi, or e at any time measured but did induce PKC-Ç 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.

Original languageEnglish (US)
Pages (from-to)F108-F113
JournalAmerican Journal of Physiology
Volume271
Issue number1 PART 2
DOIs
StatePublished - 1996

Keywords

  • Interleukin-1
  • Mesangial cells
  • Platelet-derived growth factor
  • Protein kinase C isoforms

ASJC Scopus subject areas

  • Physiology (medical)

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