Autophagy is a regulator of TGF-β1-induced fibrogenesis in primary human atrial myofibroblasts

Cell Death & Disease
S GhavamiI M C Dixon

Abstract

Transforming growth factor-β(1) (TGF-β(1)) is an important regulator of fibrogenesis in heart disease. In many other cellular systems, TGF-β(1) may also induce autophagy, but a link between its fibrogenic and autophagic effects is unknown. Thus we tested whether or not TGF-β(1)-induced autophagy has a regulatory function on fibrosis in human atrial myofibroblasts (hATMyofbs). Primary hATMyofbs were treated with TGF-β(1) to assess for fibrogenic and autophagic responses. Using immunoblotting, immunofluorescence and transmission electron microscopic analyses, we found that TGF-β(1) promoted collagen type Iα2 and fibronectin synthesis in hATMyofbs and that this was paralleled by an increase in autophagic activation in these cells. Pharmacological inhibition of autophagy by bafilomycin-A1 and 3-methyladenine decreased the fibrotic response in hATMyofb cells. ATG7 knockdown in hATMyofbs and ATG5 knockout (mouse embryonic fibroblast) fibroblasts decreased the fibrotic effect of TGF-β(1) in experimental versus control cells. Furthermore, using a coronary artery ligation model of myocardial infarction in rats, we observed increases in the levels of protein markers of fibrosis, autophagy and Smad2 phosphorylation in whole scar tissue ly...Continue Reading

References

Aug 1, 1992·Mechanisms of Development·G L EngelmannF W Ruscetti
Mar 1, 1990·Circulation Research·I M DixonN S Dhalla
Jan 1, 1988·Growth Factors·N L ThompsonM B Sporn
Jan 1, 1995·Annual Review of Physiology·J M PfefferM A Pfeffer
Feb 1, 1996·Circulation Research·T Brand, M D Schneider
Mar 21, 2000·Journal of Molecular and Cellular Cardiology·W W Brooks, C H Conrad
Sep 26, 2000·Molecular Genetics and Metabolism·P J LijnenR H Fagard
Nov 22, 2000·American Journal of Physiology. Heart and Circulatory Physiology·J HaoI M Dixon
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·J Massagué
Apr 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Baiqiu WangIan M C Dixon
Dec 31, 2002·Journal of Molecular and Cellular Cardiology·Arantxa GonzálezJavier Díez
Apr 8, 2004·Developmental Cell·Beth Levine, Daniel J Klionsky
Aug 16, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Lindsay Brown
Dec 29, 2007·The Journal of Pathology·T A Wynn
Jan 24, 2008·Autophagy·Deborah L Berry, Eric H Baehrecke
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
Sep 2, 2008·Autophagy·Daniel J KlionskyDavid C Rubinsztein
Apr 7, 2009·Nature Reviews. Gastroenterology & Hepatology·Florian Rieder, Claudio Fiocchi
Jun 9, 2009·Cardiovascular Research·Karin R SipidoVirginija Dambrauskaite
Aug 6, 2009·Annual Review of Genetics·Congcong He, Daniel J Klionsky
Sep 16, 2009·Journal of Molecular and Cellular Cardiology·Jason PellmanFarah Sheikh
Dec 22, 2009·Current Opinion in Cell Biology·Nathalie M Mazure, Jacques Pouysségur
Jan 22, 2010·American Journal of Physiology. Cell Physiology·Maryam MehrpourPatrice Codogno
Jan 23, 2010·Nature Reviews. Drug Discovery·R M du Bois
Feb 13, 2010·Annual Review of Physiology·Russell S WhelanRichard N Kitsis
May 27, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jon-Jon SantiagoIan M C Dixon
Oct 15, 2010·American Journal of Physiology. Cell Physiology·Ryan H CunningtonIan M C Dixon
Nov 10, 2010·Journal of Molecular and Cellular Cardiology·Marcin DobaczewskiNikolaos G Frangogiannis
Nov 30, 2010·Journal of Cardiac Failure·Shishir Murarka, Mohammad Reza Movahed
Mar 17, 2011·Cardiovascular Research·Hiromitsu KanamoriShinya Minatoguchi
Mar 23, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Hiromitsu KanamoriShinya Minatoguchi
May 7, 2011·Nature Medicine·Wajahat Z MehalScott L Friedman
Aug 2, 2011·Journal of Hepatology·Lien F R ThoenLeo A van Grunsven
Sep 6, 2011·Cytokine·James Harris
Sep 29, 2011·Cancer Chemotherapy and Pharmacology·Pei-Ming ChuShih-Hwa Chiou
Nov 2, 2011·The Journal of Allergy and Clinical Immunology·Audrey H PoonCatherine Laprise
Dec 14, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Saeid GhavamiAndrew J Halayko
Jan 24, 2012·Matrix Biology : Journal of the International Society for Matrix Biology·Deane F Mosher, Josephine C Adams
Feb 9, 2012·Chest·Michael S Lauer

❮ Previous
Next ❯

Citations

Nov 13, 2015·Archives of Biochemistry and Biophysics·Shenglan LiuJianmin Jiang
Sep 4, 2015·Allergy·Amir A ZekiSaeid Ghavami
Dec 1, 2015·The Journal of Clinical Investigation·Cinzia BolognaSilvia Deaglio
Apr 10, 2016·Journal of Molecular and Cellular Cardiology·Ashley L EadieKeith R Brunt
Jun 24, 2016·Nature Reviews. Rheumatology·Jason S Rockel, Mohit Kapoor
Oct 21, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ruhui HanChunhui Ni
Jun 17, 2016·Expert Review of Cardiovascular Therapy·Jaime A RiquelmeSergio Lavandero
Dec 3, 2016·American Journal of Physiology. Cell Physiology·Philippe GualSophie Lotersztajn
Oct 27, 2017·Journal of the American Heart Association·Marit WiersmaBianca J J M Brundel
Sep 29, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Wei SongNorbert Perrimon
May 27, 2017·Circulation Research·José Manuel Bravo-San PedroLorenzo Galluzzi
Mar 8, 2018·Cell Death and Differentiation·Wajihah MughalJoseph W Gordon
Nov 9, 2018·Molecular Genetics & Genomic Medicine·Pei ZhangBo Yan
Jan 25, 2018·Oncogenesis·Varvara PetrovaIvano Amelio
Nov 2, 2018·American Journal of Respiratory Cell and Molecular Biology·Kielan D McAlindenPawan Sharma
Apr 24, 2019·Aging and Disease·Lucy A MurthaAndrew J Boyle
Dec 31, 2015·World Journal of Gastroenterology : WJG·Behzad YeganehSaeid Ghavami
Sep 20, 2019·International Forum of Allergy & Rhinology·Jing Li, Yong Li
Nov 23, 2019·International Journal of Molecular Sciences·Juha M T HyttinenKai Kaarniranta
Jan 1, 2020·American Journal of Respiratory Cell and Molecular Biology·Kielan D McAlindenPawan Sharma
Aug 18, 2017·F1000Research·Anudeep KotaPawan Sharma
Jun 5, 2018·Heart Failure Reviews·Monika BartekovaNaranjan S Dhalla
Dec 19, 2018·Journal of Cardiovascular Translational Research·Shu ZhouYan Wang
Aug 1, 2020·Frontiers in Immunology·Jacob D PainterOmid Akbari
Apr 24, 2019·Stem Cells International·Fei HanFanyan Luo

❮ Previous
Next ❯

Methods Mentioned

BETA
lipidation
environmental stress
coronary artery bypass
X-ray

Software Mentioned

GraphPad
Graph Pad Prism

Related Concepts

Related Feeds

Atrial Filbrillation

Atrial fibrillation refers to the abnormal heart rhythm characterized by rapid and irregular beating of the atria. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Biomarkers for Cardiovascular Risk Assessment

Sensitive and accurate biomarkers used in cardiovascular risk prediction can potentially be used to manage the risk of cardiovascular disease. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here.

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.