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Olga Maltseva, Paula Folger, Dania Zekaria, Sevastiani Petridou, Sandra K. Masur; Fibroblast Growth Factor Reversal of the Corneal Myofibroblast Phenotype. Invest. Ophthalmol. Vis. Sci. 2001;42(11):2490-2495.
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purpose. Keratocytes give rise to fibroblasts and myofibroblasts in wounded
cornea. It is well established that treatment of fibroblasts with
transforming growth factor (TGF) β 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-β. As distinguished from the fibroblast phenotype, the
myofibroblast phenotype was identified by the assembly of α-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-β receptor types I and II,
cadherins, and connexin 43 by immunocytochemistry, Western blot
analysis, and immunoprecipitation and of α-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 α-SM actin protein, TGF-β 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-β
further enhanced the expression of α-SM actin mRNA and protein and
cell surface expression of TGF-β 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
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