The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance

PloS One
Lili LiPaul McLoughlin

Abstract

Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ) mice). Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ) mice. CREB(αΔ) mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ) and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ). CREB(αΔ) mice had larger lungs with reduced epithelial surface density suggesting increase...Continue Reading

References

Jan 1, 1989·The American Review of Respiratory Disease·P A MartoranaG Lungarella
Nov 1, 1982·Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology·T S HakimH K Chang
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·E HummlerG Schütz
Feb 1, 1997·Kidney International·I KvietikovaM Gassmann
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·D RudolphG Schütz
Jul 25, 1998·The Journal of Biological Chemistry·D Beitner-Johnson, D E Millhorn
Jan 15, 1999·Clinical and Experimental Pharmacology & Physiology·J Ludbrook
Mar 4, 2000·Progress in Nucleic Acid Research and Molecular Biology·D De Cesare, P Sassone-Corsi
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·C T TaylorS P Colgan
Apr 23, 2002·Nature Genetics·Theo MantamadiotisGünther Schütz
Aug 8, 2002·Kidney International·Wolfgang EberhardtJosef Pfeilschifter
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Katrina M ComerfordCormac T Taylor
Feb 4, 2003·The Journal of Physiology·Katherine HowellPaul McLoughlin
Sep 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Tetsutaro NagaokaMasahiko Oka
Nov 5, 2003·Circulation·Stuart Rich, Vallerie V McLaughlin
Feb 10, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jean-Marc HyvelinPaul McLoughlin
Feb 24, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karen A FaganIvan F McMurtry
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hyunjoo Cha-MolstadRichard H Goodman
Nov 17, 2004·Annals of Internal Medicine·John B WestUNKNOWN American Physiological Society
Nov 24, 2004·Journal of Applied Physiology·Chi-Ming Hai, Hak Rim Kim
Jun 18, 2005·Circulation Research·Jean-Marc HyvelinPaul McLoughlin
Jun 25, 2005·American Journal of Respiratory and Critical Care Medicine·Fumiaki AokiItaru Kojima
Apr 4, 2007·The Journal of Biological Chemistry·Sergio de FrutosLaura V González Bosc
Aug 12, 2008·American Journal of Respiratory and Critical Care Medicine·Martin O LeonardPaul McLoughlin
Feb 7, 2009·Journal of Applied Physiology·Arne YndestadArne K Andreassen
Apr 7, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·K HowellP McLoughlin
Jan 8, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Sara SignorelliWalter Pfaller
Jan 28, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claudia GrossmannMichael Gekle
May 8, 2010·American Journal of Respiratory Cell and Molecular Biology·Carmen FonsecaElisabetta A Renzoni
May 13, 2011·Journal of Cardiovascular Pharmacology·Dwight J KlemmChrystelle V Garat

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Methods Mentioned

BETA
transfection
genotyping
PCR
PLAT

Software Mentioned

ImageJ

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