Fate-determining mechanisms in epithelial-myofibroblast transition: major inhibitory role for Smad3.

The Journal of Cell Biology
András MassziAndrás Kapus

Abstract

Epithelial-myofibroblast (MF) transition (EMyT) is a critical process in organ fibrosis, leading to alpha-smooth muscle actin (SMA) expression in the epithelium. The mechanism underlying the activation of this myogenic program is unknown. We have shown previously that both injury to intercellular contacts and transforming growth factor beta (TGF-beta) are indispensable for SMA expression (two-hit model) and that contact disruption induces nuclear translocation of myocardin-related transcription factor (MRTF). Because the SMA promoter harbors both MRTF-responsive CC(A/T)-rich GG element (CArG) boxes and TGF-beta-responsive Smad-binding elements, we hypothesized that the myogenic program is mobilized by a synergy between MRTF and Smad3. In this study, we show that the synergy between injury and TGF-beta exclusively requires CArG elements. Surprisingly, Smad3 inhibits MRTF-driven activation of the SMA promoter, and Smad3 silencing renders injury sufficient to induce SMA expression. Furthermore, Smad3 is degraded under two-hit conditions, thereby liberating the myogenic program. Thus, Smad3 is a critical timer/delayer of MF commitment in the epithelium, and EMyT can be dissected into Smad3-promoted (mesenchymal) and Smad3-inhibited...Continue Reading

References

Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·S K MasurS Petridou
Sep 10, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·M B HautmannG K Owens
Jun 8, 2002·Biochemical and Biophysical Research Communications·Yun Zhao, Dawn A Geverd
Sep 5, 2002·Biochemical and Biophysical Research Communications·Motohide IsonoFuad N Ziyadeh
Oct 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Da-Zhi WangEric N Olson
Dec 31, 2002·American Journal of Physiology. Renal Physiology·Andras MassziAndrás Kapus
Apr 19, 2003·American Journal of Respiratory Cell and Molecular Biology·Biao HuSem H Phan
May 7, 2003·Cell·Francesc MirallesRichard Treisman
Jan 27, 2004·The American Journal of Pathology·Shizuya SaikaAnita B Roberts
Jun 25, 2004·The American Journal of Pathology·Gabriella LakosJohn Varga
Dec 30, 2004·The Journal of Biological Chemistry·Yan LiuGary K Owens
Nov 18, 2005·Cytokine & Growth Factor Reviews·Anita B RobertsKathleen C Flanders
Dec 3, 2005·Genes & Development·Joan MassaguéDavid Wotton
Dec 21, 2005·Genome Research·Qiang SunJoseph M Miano
Mar 29, 2006·The Journal of Cell Biology·Jonathan M LeeErik W Thompson
Jul 22, 2006·American Journal of Respiratory Cell and Molecular Biology·Biao HuSem H Phan
Aug 1, 2006·Investigative Ophthalmology & Visual Science·Alice BanhJudith A West-Mays
Aug 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kevin K KimHarold A Chapman
Aug 25, 2006·American Journal of Physiology. Cell Physiology·Joseph M MianoKeigi Fujiwara
Aug 30, 2006·Translational Research : the Journal of Laboratory and Clinical Medicine·Chien-An ChenHung-Chun Chen
Oct 13, 2006·Trends in Cell Biology·Guido Posern, Richard Treisman
Apr 3, 2007·The Journal of Biological Chemistry·Anne-Christine PonceletConstance E Runyan
Jun 29, 2007·Molecular Biology of the Cell·Stanislav N SamarinAsma Nusrat

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Citations

Nov 26, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Qiaodan ZhouGang Xu
Aug 18, 2012·Journal of Cardiovascular Translational Research·Eric M Small
Jul 13, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Nikolce GjorevskiCeleste M Nelson
Mar 27, 2012·Molecular & Cellular Proteomics : MCP·Davina TondeleirChristophe Ampe
Aug 3, 2012·Current Opinion in Pulmonary Medicine·Hidenori Kage, Zea Borok
Mar 20, 2010·American Journal of Physiology. Cell Physiology·Faiza WaheedKatalin Szászi
Dec 14, 2011·Journal of Biomedicine & Biotechnology·Catherine E WinbanksTim D Hewitson
Mar 31, 2012·American Journal of Respiratory Cell and Molecular Biology·Xiangwei HuangYong Zhou
Feb 26, 2013·The Journal of Clinical Investigation·Yong ZhouVictor J Thannickal
Jul 18, 2012·Proceedings of the American Thoracic Society·Boris Hinz
Aug 22, 2014·Molecular Biology of the Cell·Susana LechugaAndrei I Ivanov
Nov 7, 2015·Cytoskeleton·Sandeep M NalluriEsther W Gomez
May 3, 2012·Seminars in Cancer Biology·Aristidis Moustakas, Carl-Henrik Heldin
Mar 25, 2011·Kidney International·Susan E Quaggin, András Kapus
Nov 16, 2010·Free Radical Biology & Medicine·Abel Martin-GarridoKathy K Griendling
Jul 22, 2011·The Journal of Investigative Dermatology·Beverly J CriderJames J Tomasek
Mar 11, 2016·Journal of the American Society of Nephrology : JASN·Stephen G SzetoDarren A Yuen
Jun 17, 2011·Journal of Cellular Physiology·Elena Guillén-GómezMontserrat M Díaz-Encarnación
Aug 13, 2013·Periodontology 2000·Boris Hinz
Jan 12, 2012·British Journal of Pharmacology·Paul A InselNakon Aroonsakool
Mar 2, 2011·International Journal of Experimental Pathology·Soma Meran, Robert Steadman
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andrew S ChuRebecca G Wells
Jan 22, 2014·Journal of Cellular Physiology·Seethalakshmi HariharanArthur Roger Strauch
Sep 22, 2015·Frontiers in Medicine·Bram PiersmaMiriam Boersema
Jul 21, 2015·Experimental Eye Research·Boris Hinz
Jan 1, 2013·Tissue Barriers·Emmanuel CharbonneyAndrás Kapus
Jan 10, 2014·Molecular Biology of the Cell·Matthew RozyckiAndrás Kapus
Mar 6, 2012·The American Journal of Pathology·Boris HinzGiulio Gabbiani
Nov 28, 2012·The American Journal of Pathology·Attila FinthaAttila Sebe
Oct 11, 2011·The American Journal of Pathology·Xiangwei HuangYong Zhou

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Methods Mentioned

BETA
SMA
nuclear translocation
immunoprecipitation
ChIP
PCR
coimmunoprecipitation
transfection
GTPases
ubiquitination
restriction

Software Mentioned

Target Finder
Photoshop
QED InVivo
Quantity One
siRNA Target Finder
ImagePro Plus
Prism
GraphPad

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