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R. Khankan, C. Spee, S. He, S.J. Ryan, D.R. Hinton; Differential Effects of Connective Tissue Growth Factor (CTGF) Fragments on TGF–ß–Induced Expression of Fibronectin EDA in RPE Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2026.
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© ARVO (1962-2015); The Authors (2016-present)
The alternatively spliced embryonic isoform of fibronectin (FN–EDA) is one of the earliest extracellular matrix components expressed by RPE cells in response to injury and is considered to be a marker of TGFß action. We previously demonstrated that TGF–ß2 induces FN–EDA expression in a time– and dose–dependent manner and that CTGF synergistically enhances this effect. Here we determine the effect of CTGF fragments on TGF–ß2–induced FN–EDA expression.
Human fetal RPE cell cultures (passages 2–4) were treated with TGF–ß2 and with full length human recombinant CTGF (rhCTGF), N–terminal (rhN–CTGF), or C–terminal (rhC–CTGF) fragments. CTGF N– and C–terminal half fragments were generated by proteolysis of rhCTGF. FN–EDA mRNA and protein levels were analyzed at different time points by real–time qRT–PCR and Western blot, respectively.
As observed for full length rhCTGF, rhN–CTGF synergistically enhanced TGFß2–induced FN–EDA at the protein level but not at the mRNA level. rhC–CTGF had no effect on TGF–ß2–induced FN–EDA mRNA and protein levels. Stimulation with either rhN–CTGF or rhC–CTGF alone had no effect on FN–EDA expression.
The synergistic effect of rhCTGF on TGFß2–induced FN–EDA expression in co–stimulated RPE cells is mediated by the N–terminal domain of CTGF. These results suggest differing and critical roles for CTGF fragments in modulating TGF–ß responses.
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