PMID: 7524361Oct 1, 1994Paper

PKC and high glucose stimulate collagen alpha 1 (IV) transcriptional activity in a reporter mesangial cell line

The American Journal of Physiology
P FumoF N Ziyadeh

Abstract

Increased glomerular collagen IV mRNA in streptozotocin-diabetic rats and stimulation of matrix transcripts by high glucose levels in short-term mesangial cell culture provide evidence that stimulation of matrix synthesis is important in early diabetic glomerulopathy. To test whether transcriptional modulation of collagen IV genes is operative, we stably transfected a murine mesangial cell line with a "minigene" expressing luciferase driven by 5'-flanking and first-intron regions of the murine COL4A1 gene to assess the response to high glucose and the associated signaling pathway. Luciferase activity was stimulated in a dose- and time-dependent manner [near-maximal stimulation in 450 mg/dl glucose (G450) was more than twofold the level in 100 mg/dl (G100) at 48 h]; high concentrations of D-mannitol were without effect. Neither low (2 ng/ml) nor high doses (2 micrograms/ml) of insulin modified luciferase activity in either G100 or G450. We next studied whether activation of protein kinase C (PKC) mediates the effect of high glucose. Treatment with the active phorbol ester phorbol 12-myristate 13-acetate for 2-4 h or with a diacylglycerol analogue for 24 h significantly stimulated luciferase activity preferentially in G100; the P...Continue Reading

Citations

Aug 5, 2000·American Journal of Physiology. Renal Physiology·J NeugartenS Silbiger
Mar 16, 2001·American Journal of Physiology. Renal Physiology·C W HeiligF C Brosius
May 9, 2002·American Journal of Physiology. Renal Physiology·Catharine I Whiteside, John A Dlugosz
Aug 10, 2006·American Journal of Physiology. Renal Physiology·Giovanna GiannicoJerry Yee
Sep 21, 2000·American Journal of Physiology. Renal Physiology·L R JamesJ W Scholey
Aug 4, 2007·Kidney International. Supplement·H Noh, G L King

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