Role of the TGF-beta/Alk5 signaling pathway in monocrotaline-induced pulmonary hypertension.

American Journal of Respiratory and Critical Care Medicine
Ari ZaimanRubin M Tuder

Abstract

Pulmonary arterial hypertension is a progressive disease characterized by an elevation in the mean pulmonary artery pressure leading to right heart failure and a significant risk of death. Alterations in two transforming growth factor (TGF) signaling pathways, bone morphogenetic protein receptor II and the TGF-beta receptor I, Alk1, have been implicated in the pathogenesis of pulmonary hypertension (PH). However, the role of TGF-beta family signaling in PH and pulmonary vascular remodeling remains unclear. To determine whether inhibition of TGF-beta signaling will attenuate and reverse monocrotaline-induced PH (MCT-PH). We have used an orally active small-molecule TGF-beta receptor I inhibitor, SD-208, to determine the functional role of this pathway in MCT-PH. The development of MCT-PH was associated with increased vascular cell apoptosis, which paralleled TGF-beta signaling as documented by psmad2 expression. Inhibition of TGF-beta signaling with SD-208 significantly attenuated the development of the PH and reduced pulmonary vascular remodeling. These effects were associated with decreased early vascular cell apoptosis, adventitial cell proliferation, and matrix metalloproteinase expression. Inhibition of TGF-beta signaling w...Continue Reading

References

Jan 1, 1992·Critical Reviews in Toxicology·D W WilsonD Morin
May 1, 1992·The Journal of Clinical Investigation·M D BotneyR P Mecham
Jan 1, 1989·Journal of Clinical Pathology·A Kennedy, A K Foulis
Nov 1, 1968·Journal of Clinical Pathology·S F SullmanJ Stubbs
Oct 1, 1993·American Journal of Respiratory Cell and Molecular Biology·D W LipkeJ W Olson
Dec 29, 1998·Cell·R DerynckX H Feng
Sep 6, 2000·Nature Genetics·UNKNOWN International PPH ConsortiumR C Trembath
Dec 15, 2000·American Journal of Human Genetics·R D MachadoW C Nichols
May 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·V A FadokP M Henson
Jul 27, 2001·American Journal of Respiratory Cell and Molecular Biology·A RosendahlP Sideras
Jan 5, 2002·The European Respiratory Journal·E FrisdalM P Dortho
May 15, 2002·Immunology Letters·Aristidis MoustakasCarl Henrik Heldin
Aug 1, 2002·Pediatric Research·Stephen M BlackJeffrey R Fineman
Aug 9, 2002·Pathology, Research and Practice·Kazuhiro MatsuiVictor J Ferrans
Apr 1, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Eugenia Mata-GreenwoodStephen M Black
Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
Mar 17, 2004·Oncogene·Luisa Izzi, Liliana Attisano
Jun 29, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karen K K ShearesNicholas W Morrell
Aug 3, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hideyuki BeppuKenneth D Bloch
Sep 14, 2004·American Journal of Respiratory and Critical Care Medicine·Amy RichterRubin M Tuder
Nov 17, 2004·The Journal of Clinical Investigation·Connie M NgHarry C Dietz
Nov 25, 2004·American Journal of Physiology. Cell Physiology·Mehul ShahPravin B Sehgal
Nov 26, 2004·American Journal of Respiratory and Critical Care Medicine·Philippe BonniaudJack Gauldie
May 3, 2005·The European Respiratory Journal·H LepetitC Lafuma
Aug 18, 2005·Journal of Cell Science·Aristidis Moustakas, Carl-Henrik Heldin
Oct 4, 2005·The Journal of Clinical Investigation·Ralph Theo SchermulyFriedrich Grimminger
Apr 18, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Seiichiro SakaoNorbert F Voelkel
Jun 20, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kaori Ihida-StansburyPeter Lloyd Jones
Aug 25, 2006·The New England Journal of Medicine·Bart L LoeysHarry C Dietz
Mar 17, 2007·American Journal of Respiratory Cell and Molecular Biology·Pravin B Sehgal, Somshuvra Mukhopadhyay

❮ Previous
Next ❯

Citations

Dec 29, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Jiang XieShuang Liu
Jul 28, 2009·Seminars in Respiratory and Critical Care Medicine·Eric D AustinJohn A Phillips
May 5, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Caitlin S Thompson-TorgersonArtin A Shoukas
Jan 10, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rachel J DaviesNicholas W Morrell
May 6, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Qing Lu
Mar 10, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Qing LuSharon Rounds
Jan 13, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Daniel J AngeliniRoger A Johns
Aug 27, 2011·Circulation Research·Rasa TamosiunieneMark R Nicolls
Feb 2, 2013·American Journal of Respiratory and Critical Care Medicine·Vinayak ShenoyMohan K Raizada
Feb 2, 2010·American Journal of Respiratory Cell and Molecular Biology·Changlong ZhengDao Wen Wang
Nov 9, 2010·American Journal of Respiratory Cell and Molecular Biology·Laszlo FarkasMartin Kolb
Jul 16, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Cheuk-Kwan SunHon-Kan Yip
Jan 19, 2012·International Journal of Biological Sciences·Evangelia Pardali, Peter Ten Dijke
Jan 5, 2014·Canadian Journal of Physiology and Pharmacology·Xian-Wei LiXiao-Hui Li
Jun 3, 2014·BMC Infectious Diseases·Rita de Cassia dos Santos FerreiraMilena Oliveira Almeida
Jun 19, 2013·Clinical and Experimental Medicine·Ya-Yun WangYi-Biao Wang
May 31, 2011·Canadian Journal of Physiology and Pharmacology·Yun WangHuai-Liang Wang
May 9, 2012·Free Radical Biology & Medicine·Nicholas K H KhooEric E Kelley
Jan 27, 2015·Pulmonary Circulation·Brian B Graham, Rahul Kumar
Nov 26, 2015·Cardiovascular Research·Larissa A Shimoda, Wolfgang M Kuebler
Jul 31, 2010·The American Journal of Pathology·Brian B GrahamRubin M Tuder
Jun 21, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuanyuan GaoXiaoqun Dong
Jul 4, 2012·Heart Failure Clinics·Vedant GuptaRichard A Krasuski
Nov 1, 2016·American Journal of Respiratory and Critical Care Medicine·Lai-Ming YungPaul B Yu
Dec 31, 2016·Journal of Cellular Physiology·Rita Nogueira-FerreiraTiago Henriques-Coelho
May 5, 2017·Cardiovascular Research·Natasha M RogersJeffrey S Isenberg
Aug 22, 2018·American Journal of Respiratory and Critical Care Medicine·Brian B Graham, Paul B Yu
Oct 14, 2009·Lung·Kai K Lee, Surinder S Birring
Jul 1, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Maria Rosa GhignaKatrien Grünberg
Feb 21, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rui XiaoQinghua Hu
Aug 14, 2013·American Journal of Respiratory Cell and Molecular Biology·Paul D UptonNicholas W Morrell

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis