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Glucose-induced TGF-β 1 and TGF-β receptor-1 expression in vascular smooth muscle cells is mediated by protein kinase C-α

Item Type:Article
Title:Glucose-induced TGF-β 1 and TGF-β receptor-1 expression in vascular smooth muscle cells is mediated by protein kinase C-α
Creators Name:Lindschau, C. and Quass, P. and Menne, J. and Guler, F. and Fiebeler, A. and Leitges, M. and Luft, F.C. and Haller, H.
Abstract:Sclerosis and increased matrix expression in diabetes are mediated by glucose-induced transforming growth factor (TGF)-{beta}1 expression. The intracellular effects of high glucose occur at least in part by way of protein kinase C (PKC). We previously described a role for PKC-{alpha} in glucose-induced permeability. We now investigated the hypothesis that glucose-induced expression of TGF-{beta}1 and its receptors (TGF-{beta}-R1 and -R2) are mediated by activation of this PKC isoform. TGF-{beta}1 and TGF-{beta}-R expressions were determined in vascular smooth muscle cells (VSMCs) by immunocytochemistry and Western blotting. PKC isoforms were assessed by confocal microscopy. PKC isoforms were inhibited with antisense oligodeoxynucleotides. PKC-{alpha} was upregulated by overexpression or microinjection. High glucose (20 mmol/L) increased VSMC TGF-{beta}1 and TGF-{beta}-R1 expression but not TGF-{beta}-R2 expression. PKC inhibitors and specific PKC-{alpha} downregulation by antisense treatment prevented this effect, whereas antisense treatment against PKC-{beta}, -{epsilon}, and -{zeta} had no influence. PKC-{alpha} overexpression increased TGF-{beta}1 and TGF-{beta}-R1 expression but not TGF-{beta}-R2 expression. PKC-{alpha} microinjection into individual VSMCs also increased TGF-{beta}1 and TGF-{beta}-R immunofluorescence. Last, VSMCs from PKC-{alpha}-deficient mice did not respond to high glucose compared with VSMCs from wild-type mice. We propose that high glucose-induced TGF-{beta}1 and TGF-{beta}-R1 expression is mediated by PKC-{alpha}. Our findings suggest an autocrine feedback mechanism and a possible role for PKC-{alpha} in diabetic vascular disease.
Keywords:Glucose, Growth Substances, Protein Kinases, Diabetes, Smooth Vascular Muscle, Atherosclerosis, Animals, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:42
Number:3
Page Range:335-341
Date:September 2003
Official Publication:https://doi.org/10.1161/01.HYP.0000087839.72582.DD
PubMed:View item in PubMed

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