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1 From the Departments of Ophthalmology and Cell Biology/Anatomy, Mount Sinai School of Medicine of New York University, New York, New York; and 2 Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida.
PURPOSE. Transforming growth factor ß1 (TGF-ß) stimulates the
differentiation of myofibroblasts as indicated by the nascent
expression of 
-smooth muscle (-SM) actin protein and its
organization into stress fibers. Downstream messengers of TGF-ß in
the conversion from the fibroblast to the myofibroblast phenotype were
investigated. Whether TGF-ß increases the transcription of a second
growth factor, connective tissue growth factor 1 (CTGF), which could
mediate myofibroblast differentiation, was evaluated. CTGF, a newly
identified growth factor, is highly expressed in dermal granulation
tissue.
METHODS. In this study, primary cultures of rabbit corneal fibroblasts were exposed to growth factors to investigate CTGF mRNA and protein expression during myofibroblast differentiation. Statistical analysis was used to evaluate the impact of growth factor treatment on myofibroblast differentiation.
RESULTS. TGF-ß treatment induced both CTGF mRNA and protein in rabbit corneal
fibroblasts; in contrast, fibroblast growth factor-2 (FGF) and heparin
led to a decrease in CTGF mRNA. Addition of recombinant CTGF to rabbit
corneal fibroblast cultures did not significantly increase -SM actin
mRNA or protein nor did it appear to affect assembly of -SM actin
stress fibers.
CONCLUSIONS. This is the first study to present evidence for the induction of CTGF
by TGF-ß treatment of corneal fibroblasts. It is doubtful that CTGF
is the TGF-ß mediator of the corneal fibroblast to myofibroblast
transition because CTGF does not induce -SM actin in subconfluent
fibroblast cultures. CTGF may play a supporting role in myofibroblast
differentiation.
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