Abstract
PURPOSE. Transforming growth factor β1 (TGF-β) stimulates the differentiation of myofibroblasts as indicated by the nascent expression of α-smooth muscle (α-SM) actin protein and its organization into stress fibers. Downstream messengers of TGF-β in the conversion from the fibroblast to the myofibroblast phenotype were investigated. Whether TGF-β 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-β 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 α-SM actin mRNA or protein nor did it appear to affect assembly of α-SM actin stress fibers. CONCLUSIONS. This is the first study to present evidence for the induction of CTGF by TGF-β treatment of corneal fibroblasts. It is doubtful that CTGF is the TGF-β mediator of the corneal fibroblast to myofibroblast transition because CTGF does not induce α-SM actin in subconfluent fibroblast cultures. CTGF may play a supporting role in myofibroblast differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 2534-2541 |
| Number of pages | 8 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 42 |
| Issue number | 11 |
| State | Published - 2001 |