Endothelin-1 stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by endothelin receptor transactivation of the transforming growth factor-[beta] type I receptor

Journal of Cardiovascular Pharmacology
Peter J LittleNarin Osman

Abstract

We utilized human vascular smooth muscle cells to address the question if a G-protein-coupled receptor, the endothelin (ET) receptor, could transactivate a serine/threonine kinase receptor, specifically the transforming growth factor (TGF)-[beta] receptor, T[beta]RI. Functionality of the interaction was addressed by studying endothelin-1-stimulated proteoglycan synthesis. Signaling molecules were assessed by Western blotting and proteoglycan synthesis by [35S]sulfate and 35S-met/cys incorporation and molecular size by SDS-PAGE. Endothelin-1 treatment led to a time- and concentration-dependent increase in cytosolic phosphoSmad2C, which was inhibited by the mixed endothelin receptor antagonist bosentan and the T[beta]RI antagonist SB431542. Endothelin-1 treatment led to a time-dependent increase in nuclear phosphoSmad2C. Endothelin-1-stimulated proteoglycan synthesis was partially inhibited (40%) by SB431542 and completely blocked by bosentan. The effect of endothelin-1 to stimulate an increase in glycosaminoglycan size on biglycan was also blocked in a concentration-dependent manner by SB431542. These data extend the current paradigm of G-protein coupled receptor signaling to include the transactivation of the serine kinase rece...Continue Reading

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Citations

Feb 21, 2013·Cardiology in Review·Theofilos M KolettisYasuo Matsumura
Aug 18, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ralf BahdeSanjeev Gupta
Dec 15, 2015·Frontiers in Cardiovascular Medicine·Danielle KamatoPeter J Little
Nov 7, 2016·Cellular and Molecular Life Sciences : CMLS·Danielle KamatoPeter J Little
Feb 15, 2017·Journal of Cardiovascular Pharmacology·Allison E Schafer, Burns C Blaxall
Feb 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Muhamad A RostamPeter J Little
Feb 9, 2017·Journal of Cell Communication and Signaling·Rebecca ChaplinDanielle Kamato
Aug 14, 2019·Cellular and Molecular Life Sciences : CMLS·Danielle KamatoPeter J Little
Sep 14, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Ying ZhouDanielle Kamato
Jan 26, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Danielle Kamato, Peter J Little
Jun 23, 2020·ACS Pharmacology & Translational Science·Rizwana AfrozDanielle Kamato

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