IOVS Is this journal stale?
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 Maltseva, O.
Right arrow Articles by Masur, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maltseva, O.
Right arrow Articles by Masur, S. K.
(Investigative Ophthalmology and Visual Science. 2001;42:2490-2495.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Fibroblast Growth Factor Reversal of the Corneal Myofibroblast Phenotype

Olga Maltseva, Paula Folger, Dania Zekaria, Sevastiani Petridou and Sandra K. Masur

From the Departments of Ophthalmology and Cell Biology/Anatomy, Mount Sinai School of Medicine of New York University, New York, New York.

PURPOSE. Keratocytes give rise to fibroblasts and myofibroblasts in wounded cornea. It is well established that treatment of fibroblasts with transforming growth factor (TGF) ß will induce myofibroblast differentiation. We investigated whether this differentiation could be reversed by the administration of fibroblast growth factor (FGF).

METHODS. Cultured corneal myofibroblasts were plated at 200 cells/mm2, and cells were grown in DMEM/F12 containing (1) 10% FBS or (2) 10% FBS with FGF and heparin or (3) 1% FBS or (4) 1% FBS with TGF-ß. As distinguished from the fibroblast phenotype, the myofibroblast phenotype was identified by the assembly of {alpha}-smooth muscle (SM) actin protein into the stress fiber cytoskeleton. To further characterize growth factor regulation of the two phenotypes, the phenotypic expression of TGF-ß receptor types I and II, cadherins, and connexin 43 by immunocytochemistry, Western blot analysis, and immunoprecipitation and of {alpha}-SM actin mRNA in Northern blot analysis were evaluated.

RESULTS. Corneal myofibroblasts replated and grown in the presence of FGF-1 or FGF-2 (20 ng/ml) plus heparin (5 µg/ml) in 10% FBS medium had decreased expression of {alpha}-SM actin protein, TGF-ß receptors, and cadherins. Thus, FGF–heparin decreased the myofibroblast phenotype and promoted the fibroblast phenotype. Administration of either 20 ng/ml FGF or 5 µg/ml heparin alone was not effective. Addition of TGF-ß further enhanced the expression of {alpha}-SM actin mRNA and protein and cell surface expression of TGF-ß receptors in myofibroblast cultures.

CONCLUSIONS. FGF-1 or -2 and heparin promoted the fibroblast phenotype and reversed the myofibroblast phenotype. This finding supports the idea that corneal myofibroblasts and fibroblasts are alternative phenotypes rather than terminally differentiated cell types.




This article has been cited by other articles:


Home page
 IOVSHome page
J. He and H. E. P. Bazan
Epidermal Growth Factor Synergism with TGF-{beta}1 via PI-3 Kinase Activity in Corneal Keratocyte Differentiation
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2936 - 2945.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. C. Cushing, P. D. Mariner, J.-T. Liao, E. A. Sims, and K. S. Anseth
Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells
FASEB J, June 1, 2008; 22(6): 1769 - 1777.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. Ebihara, S. Yamagami, L. Chen, T. Tokura, M. Iwatsu, H. Ushio, and A. Murakami
Expression and Function of Toll-like Receptor-3 and -9 in Human Corneal Myofibroblasts
Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3069 - 3076.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
G Perrella, P Brusini, R Spelat, P Hossain, A Hopkinson, and H S Dua
Expression of haematopoietic stem cell markers, CD133 and CD34 on human corneal keratocytes
Br. J. Ophthalmol., January 1, 2007; 91(1): 94 - 99.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Ramos, M. Montano, C. Becerril, J. Cisneros-Lira, L. Barrera, V. Ruiz, A. Pardo, and M. Selman
Acidic fibroblast growth factor decreases {alpha}-smooth muscle actin expression and induces apoptosis in human normal lung fibroblasts
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L871 - L879.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C. K. Sen, S. Khanna, and S. Roy
Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart
Cardiovasc Res, July 15, 2006; 71(2): 280 - 288.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. He and H. E. P. Bazan
Synergistic Effect of Platelet-Activating Factor and Tumor Necrosis Factor-{alpha} on Corneal Myofibroblast Apoptosis.
Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 883 - 891.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
E. M. Espana, T. Kawakita, M. A. Di Pascuale, W. Li, L.-K. Yeh, J.-M. Parel, C.-Y. Liu, and S. C. G. Tseng
The Heterogeneous Murine Corneal Stromal Cell Populations In Vitro
Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4528 - 4535.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Taliana, M. Benezra, R. S. Greenberg, S. K. Masur, and A. M. Bernstein
ZO-1: Lamellipodial Localization in a Corneal Fibroblast Wound Model
Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 96 - 103.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
E. M. Espana, T. Kawakita, C.-Y. Liu, and S. C. G. Tseng
CD-34 Expression by Cultured Human Keratocytes Is Downregulated during Myofibroblast Differentiation Induced by TGF-{beta}1
Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 2985 - 2991.
[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
 IOVSHome page
D. G. Ryan, L. Taliana, L. Sun, Z.-G. Wei, S. K. Masur, and R. M. Lavker
Involvement of S100A4 in Stromal Fibroblasts of the Regenerating Cornea
Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4255 - 4262.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Wu, C. Jin, F. Wang, C. Yu, and W. L. McKeehan
Stromal Cell Heterogeneity in Fibroblast Growth Factor-mediated Stromal-Epithelial Cell Cross-Talk in Premalignant Prostate Tumors
Cancer Res., August 15, 2003; 63(16): 4936 - 4944.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. L. Berryhill, R. Kader, B. Kane, D. E. Birk, J. Feng, and J. R. Hassell
Partial Restoration of the Keratocyte Phenotype to Bovine Keratocytes Made Fibroblastic by Serum
Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3416 - 3421.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Wang, L. D. Carbone, and M. A. Watsky
Receptor-Mediated Activation of a Cl- Current by LPA and S1P in Cultured Corneal Keratocytes
Invest. Ophthalmol. Vis. Sci., October 1, 2002; 43(10): 3202 - 3208.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
P. A. Folger, D. Zekaria, G. Grotendorst, and S. K. Masur
Transforming Growth Factor-{beta}-Stimulated Connective Tissue Growth Factor Expression during Corneal Myofibroblast Differentiation
Invest. Ophthalmol. Vis. Sci., October 1, 2001; 42(11): 2534 - 2541.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Association for Research in Vision and Ophthalmology