Stimulation of endothelin-1 gene expression by insulin via phosphoinositide-3 kinase-glycogen synthase kinase-3beta signaling in endothelial cells

Life Sciences
Zeran Yang, Ji-Cheng Li

Abstract

Insulin stimulates secretion of the potent vasoactive and mitogenic peptide endothelin-1 (ET-1) from endothelial cells. We sought to investigate whether phosphoinositide-3 kinase (PI3K)-dependent inactivation of glycogen synthase kinase-3beta (GSK3beta) by insulin leads to elevation of ET-1 gene expression in endothelial cells. Inhibition of GSK3beta activity by LiCl or siRNA technique mimicked insulin action to stimulate ET-1 gene expression. Luciferase reporter assay showed insulin stimulated-elevation of ET-1 promoter activity can be abolished by the PI3K inhibitor Wortmannin, but not by the mitogen activated protein kinase (MAPK) inhibitor PD-98059. To further investigate whether the transcription factor vascular endothelial zinc finger-1 (Vezf1) is involved in ET-1 regulation, site-mutated reporter plasmid was used in luciferase reporter assay. A 2-bp mutation in Vezf1 binding element abolished insulin-stimulated elevation of ET-1 promoter activity. Furthermore, siRNA inhibition of Vezf1 led to decline in the levels of ET-1 mRNA and ET-1 peptides. These observations indicate that PI3K-dependent inactivation of GSK3beta by insulin leads to upregulation of ET-1 gene expression and Vezf1 may be a target for ET-1 regulation by...Continue Reading

References

Aug 1, 1995·Molecular and Cellular Biology·M KawanaT Quertermous
Aug 1, 1993·Metabolism: Clinical and Experimental·H A WolpertD C Simonson
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·H Eldar-Finkelman, E G Krebs
Jun 11, 1999·The Journal of Biological Chemistry·S A SummersM J Birnbaum
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·X FangG B Mills
Jun 8, 2001·QJM : Monthly Journal of the Association of Physicians·R J IrvingB R Walker
Sep 21, 2001·The Biochemical Journal·S Frame, P Cohen
Nov 1, 2001·Respiratory Research·K A FaganD M Rodman
Mar 9, 2002·Advances in Cancer Research·Armen S Manoukian, James R Woodgett
Mar 5, 2003·Journal of Cell Science·Bradley W Doble, James R Woodgett
Mar 7, 2003·American Journal of Hypertension·Michiko NagaiToshio Ogihara
May 3, 2003·The Journal of Clinical Investigation·David VicentC Ronald Kahn
Jul 4, 2003·Canadian Journal of Physiology and Pharmacology·Nicolas Bousette, Adel Giaid
Mar 17, 2004·The Journal of Biological Chemistry·Ashour MichaelThomas Force
Apr 3, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Etto C EringaPieter Sipkema
Jul 1, 2004·American Journal of Physiology. Endocrinology and Metabolism·Chi-Chang JuanLow-Tone Ho
Apr 20, 2005·Journal of Cardiovascular Pharmacology·Fernando Rodríguez-PascualSantiago Lamas
May 11, 2005·Developmental Biology·Frank KuhnertHeidi Stuhlmann
Nov 4, 2005·Acta Physiologica Scandinavica·M IemitsuH Tanaka
Aug 17, 2006·The Journal of Biological Chemistry·Min-Huei Liang, De-Maw Chuang

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Citations

Dec 23, 2011·Basic Research in Cardiology·Hanrui ZhangCuihua Zhang
Oct 17, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Kevin E C Meyers, Christine Sethna
Jul 24, 2008·Nature Clinical Practice. Nephrology·Matthias Barton
Sep 15, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lisa R StowBrian D Cain
Jan 7, 2010·Current Opinion in Nephrology and Hypertension·Donald E Kohan
Aug 30, 2012·The American Journal of Chinese Medicine·Sun Mi HwangHo Sub Lee
Nov 20, 2013·International Journal of Biological Sciences·Peramaiyan RajendranIkuo Nishigaki
Nov 1, 2008·Endocrinology·Mogher KhamaisiItamar Raz
May 26, 2018·The Journal of Biological Chemistry·Lama AlAbdiHumaira Gowher
Jun 26, 2012·FEBS Letters·Sanjaya Kuruppu, A Ian Smith
Feb 8, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Fernando Rodríguez-PascualSantiago Lamas

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