IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 You, L.
Right arrow Articles by Kruse, F. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by You, L.
Right arrow Articles by Kruse, F. E.
(Investigative Ophthalmology and Visual Science. 2002;43:72-81.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Differential Effect of Activin A and BMP-7 on Myofibroblast Differentiation and the Role of the Smad Signaling Pathway

Lingtao You and Friedrich E. Kruse

From the Department of Ophthalmology, University of Heidelberg Medical School, Heidelberg, Germany.

PURPOSE. To investigate myofibroblast differentiation and signal transduction induced by TGF-ß family members activin A and bone morphogenetic protein (BMP)-7.

METHODS. Transcription of activin and receptors (ActR) for activin A and BMP-7 was detected by RT-PCR. Levels of marker proteins for differentiation and phosphorylation of similar to mothers against decapentaplegics (Smads) were quantified by Western blot analysis in response to BMP-7, activin A and follistatin. Transfection with antisense Smad2/3 was performed to evaluate signal transduction.

RESULTS. Activin A and receptors (ActR-I, ActR-IB, ActR-II) are transcribed in corneal fibroblasts. Compared with TGF-ß1 or serum, activin A but not BMP-7 increased {alpha}-smooth muscle (SM) actin and actin-binding proteins such as SM myosin, {alpha}-actinin, and vinculin. Talin, paxillin, and desmin were not induced and vimentin was downregulated by activin. Activin also induced extracellular matrix proteins fibronectin and integrin ß1. Activin-dependent accumulation of proteins was blocked by follistatin. Regarding signal transduction, activin A induced phosphorylation of Smad 2, and BMP-7 induced Smad 1, both of which were inhibited by follistatin. Transfection with antisense Smad 2/3 prevented activin-induced expression and accumulation of {alpha}-SM actin.

CONCLUSIONS. TGF-ß proteins have different functions in the cornea. Activin A and TGF-ß1, but not BMP-7, are regulators of corneal keratocyte differentiation and may play a role during myofibroblast transdifferentiation. Smad 2/3 signal transduction seems to be important in the regulation of muscle-specific genes. Further investigation of Smad signaling may help to better understand the function of TGF-ß family members in the cornea.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
K. Fu, M. J. Corbley, L. Sun, J. E. Friedman, F. Shan, J. L. Papadatos, D. Costa, F. Lutterodt, H. Sweigard, S. Bowes, et al.
SM16, an Orally Active TGF-{beta} Type I Receptor Inhibitor Prevents Myofibroblast Induction and Vascular Fibrosis in the Rat Carotid Injury Model
Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 665 - 671.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
R. J. Wordinger and A. F. Clark
Bone Morphogenetic Proteins and Their Receptors in the Eye
Experimental Biology and Medicine, September 1, 2007; 232(8): 979 - 992.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. K. Mouw, J. T. Connelly, C. G. Wilson, K. E. Michael, and M. E. Levenston
Dynamic Compression Regulates the Expression and Synthesis of Chondrocyte-Specific Matrix Molecules in Bone Marrow Stromal Cells
Stem Cells, March 1, 2007; 25(3): 655 - 663.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Saika, K. Ikeda, O. Yamanaka, T. Miyamoto, Y. Ohnishi, M. Sato, Y. Muragaki, A. Ooshima, Y. Nakajima, W. W.-Y. Kao, et al.
Expression of Smad7 in Mouse Eyes Accelerates Healing of Corneal Tissue after Exposure to Alkali
Am. J. Pathol., May 1, 2005; 166(5): 1405 - 1418.
[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
 J. Med. Genet.Home page
C Y Gregory-Evans, M J Williams, S Halford, and K Gregory-Evans
Ocular coloboma: a reassessment in the age of molecular neuroscience
J. Med. Genet., December 1, 2004; 41(12): 881 - 891.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. A. K. Harvey, S. C. Anderson, and N. SundarRaj
Downstream Effects of ROCK Signaling in Cultured Human Corneal Stromal Cells: Microarray Analysis of Gene Expression
Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2168 - 2176.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
V. Poulaki, N. Mitsiades, F. E. Kruse, S. Radetzky, E. Iliaki, B. Kirchhof, and A. M. Joussen
Activin A in the Regulation of Corneal Neovascularization and Vascular Endothelial Growth Factor Expression
Am. J. Pathol., April 1, 2004; 164(4): 1293 - 1302.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. V. Jester, J. Huang, S. Fisher, J. Spiekerman, J. H. Chang, W. E. Wright, and J. W. Shay
Myofibroblast Differentiation of Normal Human Keratocytes and hTERT, Extended-Life Human Corneal Fibroblasts
Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1850 - 1858.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Association for Research in Vision and Ophthalmology