help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on April 17, 2003, doi:10.1165/rcmb.2003-0063OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0063OCv1
29/3/397    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hu, B.
Right arrow Articles by Phan, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, B.
Right arrow Articles by Phan, S. H.
American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 397-404, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2003-0063OC

Smad3 Mediates Transforming Growth Factor-ß–Induced {alpha}-Smooth Muscle Actin Expression

Biao Hu, Zhe Wu and Sem H. Phan

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan

Address correspondence to: Dr. Sem H. Phan, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602. E-mail: shphan{at}umich.edu

Transforming growth factor-ß (TGF-ß)–induced {alpha}-smooth muscle actin (ASMA) expression is a key indicator of myofibroblast differentiation from fibroblasts. Recent studies suggest that a TGF-ß control element is important in the regulation of the ASMA gene promoter by TGF-ß. In this study, the role of Smad3, a key component of the Smad pathway that mediates TGF-ß signaling in regulation of ASMA gene expression, is investigated. All members of the Smad family were expressed in rat lung fibroblasts, and Smad3 expression was elevated upon TGF-ß1 treatment. Transfection with a Smad3-expressing plasmid markedly increased Smad3 and ASMA protein expression, whereas transfection with an antisense Smad3 plasmid suppressed Smad3 and ASMA expression. Similar effects were noted when the cloned rat ASMA promoter-luciferase reporter gene construct was used to monitor transcriptional activation of the ASMA gene. Electrophoretic mobility shift assays and DNA affinity precipitation indicated Smad3 binding to at least two regions of the promoter containing CAGA motifs, termed Smad3-binding elements (SBEs). Mutation of one of the SBEs decreased promoter activity significantly, indicative of a functional role for this SBE. Taken together, these findings suggest a role for Smad3 in TGF-ß regulation of ASMA gene expression in myofibroblast differentiation.

Abbreviations: {alpha}-smooth muscle actin, ASMA • Dulbecco's modified Eagle's medium, DMEM • electrophoretic mobility shift assay, EMSA • phosphate-buffered saline, PBS • plasma-derived serum, PDS • phenylmethylsulfonyl fluoride, PMSF • Smad3-binding element, SBE • TGF-ß control element, TCE • transforming growth factor-ß, TGF-ß




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
A. Sebe, S.-K. Leivonen, A. Fintha, A. Masszi, L. Rosivall, V.-M. Kahari, and I. Mucsi
Transforming growth factor-{beta}-induced alpha-smooth muscle cell actin expression in renal proximal tubular cells is regulated by p38{beta} mitogen-activated protein kinase, extracellular signal-regulated protein kinase1,2 and the Smad signalling during epithelial-myofibroblast transdifferentiation
Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1537 - 1545.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
S. H. Phan
Biology of Fibroblasts and Myofibroblasts
Proceedings of the ATS, April 15, 2008; 5(3): 334 - 337.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, M. Cho, D.-S. Suh, M.-S. Yoon, C. L. Chang, J. S. Jung, et al.
Cancer-Derived Lysophosphatidic Acid Stimulates Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells
Stem Cells, March 1, 2008; 26(3): 789 - 797.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Ishida, J.-L. Gao, and P. M. Murphy
Chemokine Receptor CX3CR1 Mediates Skin Wound Healing by Promoting Macrophage and Fibroblast Accumulation and Function
J. Immunol., January 1, 2008; 180(1): 569 - 579.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. O. Mitchell and D. M. Guidot
Alcohol Ingestion by Donors Amplifies Experimental Airway Disease after Heterotopic Transplantation
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1161 - 1168.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Kono, T. Nishiuma, Y. Nishimura, Y. Kotani, T. Okada, S.-i. Nakamura, and M. Yokoyama
Sphingosine Kinase 1 Regulates Differentiation of Human and Mouse Lung Fibroblasts Mediated by TGF-beta1
Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 395 - 404.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. T. Freddie, Z. Ji, A. Marais, and A. D. Sharrocks
Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRF
Nucleic Acids Res., August 1, 2007; (2007) gkm528v1.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. Y. Liu, D. D. Swartz, H. F. Peng, S. F. Gugino, J. A. Russell, and S. T. Andreadis
Functional tissue-engineered blood vessels from bone marrow progenitor cells
Cardiovasc Res, August 1, 2007; 75(3): 618 - 628.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. V. Le, J. Y. Cho, M. Miller, S. McElwain, K. Golgotiu, and D. H. Broide
Inhibition of Allergen-Induced Airway Remodeling in Smad 3-Deficient Mice
J. Immunol., June 1, 2007; 178(11): 7310 - 7316.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. Vittal, H. Zhang, M. K. Han, B. B. Moore, J. C. Horowitz, and V. J. Thannickal
Effects of the Protein Kinase Inhibitor, Imatinib Mesylate, on Epithelial/Mesenchymal Phenotypes: Implications for Treatment of Fibrotic Diseases
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 35 - 44.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
L. Fan, A. Sebe, Z. Peterfi, A. Masszi, A. C.P. Thirone, O. D. Rotstein, H. Nakano, C. A. McCulloch, K. Szaszi, I. Mucsi, et al.
Cell Contact-dependent Regulation of Epithelial-Myofibroblast Transition via the Rho-Rho Kinase-Phospho-Myosin Pathway
Mol. Biol. Cell, March 1, 2007; 18(3): 1083 - 1097.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
Y. Sheffer, O. Leon, J. H. Pinthus, A. Nagler, Y. Mor, O. Genin, M. Iluz, N. Kawada, K. Yoshizato, and M. Pines
Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
Mol. Cancer Ther., February 1, 2007; 6(2): 570 - 577.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. Hu, Z. Wu, T. Liu, M. R. Ullenbruch, H. Jin, and S. H. Phan
Gut-Enriched Kruppel-Like Factor Interaction with Smad3 Inhibits Myofibroblast Differentiation
Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 78 - 84.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. D. Keller, P. Rivera Gil, M. Tolle, M. van der Giet, J. Chun, H. H. Radeke, M. Schafer-Korting, and B. Kleuser
Immunomodulator FTY720 Induces Myofibroblast Differentiation via the Lysophospholipid Receptor S1P3 and Smad3 Signaling
Am. J. Pathol., January 1, 2007; 170(1): 281 - 292.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, Y. C. Bae, J. S. Jung, and J. H. Kim
Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-{beta}-dependent mechanism
J. Cell Sci., December 1, 2006; 119(23): 4994 - 5005.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. Li, N. V. Campanale, R. J. Liang, J. A. Deane, J. F. Bertram, and S. D. Ricardo
Inhibition of p38 Mitogen-Activated Protein Kinase and Transforming Growth Factor-{beta}1/Smad Signaling Pathways Modulates the Development of Fibrosis in Adriamycin-Induced Nephropathy
Am. J. Pathol., November 1, 2006; 169(5): 1527 - 1540.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
C. R. Montague, M. G. Hunter, M. A. Gavrilin, G. S. Phillips, P. J. Goldschmidt-Clermont, and C. B. Marsh
Activation of Estrogen Receptor-{alpha} Reduces Aortic Smooth Muscle Differentiation
Circ. Res., September 1, 2006; 99(5): 477 - 484.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. Liu, B. Hu, M. J. Chung, M. Ullenbruch, H. Jin, and S. H. Phan
Telomerase Regulation of Myofibroblast Differentiation
Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 625 - 633.
[Abstract] [Full Text] [PDF]

Home page
 PERSPECT VASC SURG ENDOVASC THERHome page
B. J. Faler, R. A. Macsata, D. Plummer, L. Mishra, and A. N. Sidawy
Transforming Growth Factor-{beta} and Wound Healing
Perspectives in Vascular Surgery and Endovascular Therapy, March 1, 2006; 18(1): 55 - 62.
[Abstract] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Jinnin, H. Ihn, and K. Tamaki
Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-beta1-Induced Extracellular Matrix Expression
Mol. Pharmacol., February 1, 2006; 69(2): 597 - 607.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
B. C. Willis, R. M. duBois, and Z. Borok
Epithelial Origin of Myofibroblasts during Fibrosis in the Lung.
Proceedings of the ATS, January 1, 2006; 3(4): 377 - 382.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. F. Clem and B. J. Clark
Association of the mSin3A-Histone Deacetylase 1/2 Corepressor Complex with the Mouse Steroidogenic Acute Regulatory Protein Gene
Mol. Endocrinol., January 1, 2006; 20(1): 100 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. S. White, R. G. Atrasz, B. Hu, S. H. Phan, V. Stambolic, T. W. Mak, C. M. Hogaboam, K. R. Flaherty, F. J. Martinez, C. D. Kontos, et al.
Negative Regulation of Myofibroblast Differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10)
Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 112 - 121.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
P. Qiu, R. P. Ritchie, Z. Fu, D. Cao, J. Cumming, J. M. Miano, D.-Z. Wang, H. J. Li, and L. Li
Myocardin Enhances Smad3-Mediated Transforming Growth Factor-{beta}1 Signaling in a CArG Box-Independent Manner: Smad-Binding Element Is an Important cis Element for SM22{alpha} Transcription In Vivo
Circ. Res., November 11, 2005; 97(10): 983 - 991.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. S. Tan, L. Michalik, B. Desvergne, and W. Wahli
Genetic- or Transforming Growth Factor-{beta}1-induced Changes in Epidermal Peroxisome Proliferator-activated Receptor {beta}/{delta} Expression Dictate Wound Repair Kinetics
J. Biol. Chem., May 6, 2005; 280(18): 18163 - 18170.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. K. Jeffery, P. D. Upton, R. C. Trembath, and N. W. Morrell
BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways
Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L370 - L378.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. S. Swaney, D. M. Roth, E. R. Olson, J. E. Naugle, J. G. Meszaros, and P. A. Insel
Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase
PNAS, January 11, 2005; 102(2): 437 - 442.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Wang, M. C. Wilkes, E. B. Leof, and R. Hirschberg
Imatinib mesylate blocks a non-Smad TGF-{beta} pathway and reduces renal fibrogenesis in vivo
FASEB J, January 1, 2005; 19(1): 1 - 11.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Hu, Z. Wu, H. Jin, N. Hashimoto, T. Liu, and S. H. Phan
CCAAT/Enhancer-Binding Protein {beta} Isoforms and the Regulation of {alpha}-Smooth Muscle Actin Gene Expression by IL-1{beta}
J. Immunol., October 1, 2004; 173(7): 4661 - 4668.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society.