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(Hypertension. 2003;42:335.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Glucose-Induced TGF-ß1 and TGF-ß Receptor-1 Expression in Vascular Smooth Muscle Cells Is Mediated by Protein Kinase C-

Carsten Lindschau; Petra Quass; Jan Menne; Faikah Güler; Anette Fiebeler; Michael Leitges; Friedrich C. Luft; Hermann Haller

From the Department of Nephrology, Medical School Hannover (C.L., P.Q., J.M., F.G., A.F., H.H.), Hannover; the Max-Planck Institute for Experimental Endocrinology (M.L.), Hannover; and Helios-Klinikum, Franz Volhard Clinic, and the Max Delbrück Center for Molecular Medicine (F.C.L.), Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany.

Correspondence to Hermann Haller, MD, Department of Nephrology, OE 6840, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. E-mail haller.hermann{at}mh-hannover.de

Sclerosis and increased matrix expression in diabetes are mediated by glucose-induced transforming growth factor (TGF)-ß1 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- in glucose-induced permeability. We now investigated the hypothesis that glucose-induced expression of TGF-ß1 and its receptors (TGF-ß-R1 and -R2) are mediated by activation of this PKC isoform. TGF-ß1 and TGF-ß-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- was upregulated by overexpression or microinjection. High glucose (20 mmol/L) increased VSMC TGF-ß1 and TGF-ß-R1 expression but not TGF-ß-R2 expression. PKC inhibitors and specific PKC- downregulation by antisense treatment prevented this effect, whereas antisense treatment against PKC-ß, -, and - had no influence. PKC- overexpression increased TGF-ß1 and TGF-ß-R1 expression but not TGF-ß-R2 expression. PKC- microinjection into individual VSMCs also increased TGF-ß1 and TGF-ß-R immunofluorescence. Last, VSMCs from PKC--deficient mice did not respond to high glucose compared with VSMCs from wild-type mice. We propose that high glucose-induced TGF-ß1 and TGF-ß-R1 expression is mediated by PKC-. Our findings suggest an autocrine feedback mechanism and a possible role for PKC- in diabetic vascular disease.

Key Words: glucose • growth substances • protein kinases • diabetes • muscle, vascular, smooth • atherosclerosis

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