Prostaglandin E2 inhibits specific lung fibroblast functions via selective actions of PKA and Epac-1.

American Journal of Respiratory Cell and Molecular Biology
Steven K HuangMarc Peters-Golden

Abstract

Via their capacities for proliferation and synthesis of matrix proteins such as collagen, fibroblasts are key effectors in the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis. Prostaglandin E(2) (PGE(2)) potently inhibits these functions in lung fibroblasts through receptor ligation and production of the second messenger cAMP, but the downstream pathways mediating such actions have not been fully characterized. We sought to investigate the roles of the cAMP effectors protein kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1) in modulating these two functions in primary human fetal lung IMR-90 fibroblasts. The specific roles of these two effector pathways were examined by treating cells with PKA-specific (6-bnz-cAMP) and Epac-specific (8-pCPT-2'-O-Me-cAMP) agonists, inhibiting PKA with the inhibitor KT 5720, overexpressing the PKA catalytic subunit, and silencing Epac-1 using short hairpin RNA. PGE(2) inhibition of collagen I expression was mediated exclusively by activation of PKA, while inhibition of fibroblast proliferation was mediated exclusively by activation of Epac-1. PGE(2) and Epac-1 inhibited cell proliferation through activation of the small GTPase Rap1, since decreasing Rap1 ac...Continue Reading

References

Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·A B RobertsM B Sporn
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J Blenis
Dec 18, 1998·Science·H KawasakiA M Graybiel
Aug 28, 1999·The Journal of Biological Chemistry·L L DuganD H Gutmann
Feb 15, 2001·Annals of Internal Medicine·M SelmanUNKNOWN American College of Chest Physicians
Nov 7, 2001·The Journal of Clinical Investigation·S A JimenezJ Rosenbloom
Jan 24, 2002·Molecular Cell·John M Schmitt, Philip J S Stork
Jun 18, 2002·FEBS Letters·Juha-Pekka PursiheimoMarkku Salmivirta
Jun 21, 2002·Trends in Cell Biology·Philip J S Stork, John M Schmitt
May 10, 2003·American Journal of Respiratory Cell and Molecular Biology·Jill E KolodsickBethany B Moore
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Johannes L Bos
Nov 11, 2003·American Journal of Respiratory and Critical Care Medicine·Marc Peters-Golden
Apr 13, 2004·American Journal of Physiology. Cell Physiology·Xiaoqiu LiuPaul A Insel
Jun 19, 2004·The Biochemical Journal·Maria M MagieraStephen J Yarwood
Oct 29, 2004·The American Journal of Pathology·Rebecca J HodgesRobin J McAnulty
Nov 13, 2004·American Journal of Respiratory Cell and Molecular Biology·Eric S WhiteMarc Peters-Golden
Mar 3, 2005·Nucleic Acids Research·Masatoshi JinninKunihiko Tamaki
Oct 7, 2005·Molecular Biology of the Cell·Simone KiermayerAlbrecht Piiper
Oct 10, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Steven HuangMarc Peters-Golden
Jun 23, 2007·American Journal of Respiratory Cell and Molecular Biology·Carlos H SerezaniMarc Peters-Golden
Oct 6, 2007·American Journal of Respiratory and Critical Care Medicine·Steven K HuangMarc Peters-Golden
Nov 13, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karen M KasselMyron L Toews
Dec 8, 2007·The Journal of Biological Chemistry·Daniel HochbaumDaniel L Altschuler

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Citations

May 24, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·F LamyelKurt Racké
Jul 29, 2011·The Journal of Biological Chemistry·Katsuhide OkunishiMarc Peters-Golden
Sep 2, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Huandong YanRaymond B Penn
May 31, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Steven K HuangMarc Peters-Golden
Mar 30, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xiaoqiu LiuRennolds S Ostrom
Apr 25, 2012·Mediators of Inflammation·Beatriz Sastre, Victoria del Pozo
Jun 5, 2010·American Journal of Respiratory and Critical Care Medicine·Tadashi SatoStephen I Rennard
Jan 19, 2013·American Journal of Respiratory and Critical Care Medicine·Maylis DagouassatJorge Boczkowski
Jan 20, 2009·American Journal of Respiratory Cell and Molecular Biology·Nathan SandboNickolai O Dulin
Mar 23, 2011·American Journal of Respiratory Cell and Molecular Biology·Paul D Bozyk, Bethany B Moore
Mar 9, 2013·American Journal of Respiratory Cell and Molecular Biology·Garth GarrisonMarc Peters-Golden
Apr 24, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bo WeiXinmin Liu
Sep 10, 2013·Pulmonary Circulation·Roberto Sessa, Akiko Hata
Jun 23, 2015·American Journal of Respiratory Cell and Molecular Biology·Scott H WettlauferSteven K Huang
Mar 30, 2013·Journal of Pharmacological Sciences·Shinya AyabeTakahisa Murata
Oct 22, 2015·American Journal of Respiratory Cell and Molecular Biology·Qiyuan ZhouGuofei Zhou
Mar 1, 2012·Clinics in Chest Medicine·Toby M Maher
Oct 23, 2009·British Journal of Pharmacology·Terence Peters, Peter J Henry
Mar 15, 2018·Physiological Reviews·William G Robichaux, Xiaodong Cheng
Jul 22, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Scott H WettlauferMarc Peters-Golden
Dec 19, 2018·American Journal of Respiratory Cell and Molecular Biology·Steven K Huang
Aug 23, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ryan T DackorDarryl C Zeldin
Jan 12, 2012·British Journal of Pharmacology·Paul A InselNakon Aroonsakool
Apr 16, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jacob KachNickolai O Dulin
Jun 20, 2017·Current Medicinal Chemistry·Sergei N OrlovNickolai O Dulin
Nov 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Takeo NakanishiIkumi Tamai
Sep 3, 2017·The Journal of Pharmacology and Experimental Therapeutics·Marlies SchippersKlaas Poelstra
Jun 19, 2013·Pharmacological Reviews·Utako YokoyamaYoshihiro Ishikawa
Sep 20, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhong-Bin DengHuang-Ge Zhang
Sep 28, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katsuhide OkunishiMarc Peters-Golden
Nov 10, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Miguel Perez-AsoBruce N Cronstein
Sep 30, 2019·Cellular and Molecular Life Sciences : CMLS·Loka R Penke, Marc Peters-Golden
Nov 17, 2009·British Journal of Pharmacology·Maria GrandochMartina Schmidt
May 23, 2015·Thorax·Elise G De SmetKen R Bracke

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