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A. Ohlmann, R. Fuchshofer, A.V. Ohlmann, N. Pfeiffer; Induction of Thrombospondin–1 and Connective Tissue Growth Factor in Human Tenon Fibroblasts by Transforming Growth Factor–ß and Dexamethasone . Invest. Ophthalmol. Vis. Sci. 2005;46(13):54.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the expression of Thrombospondin–1 (TSP–1) and connective tissue growth factor (CTGF) in human tenon fibroblasts (TF). The main reason for failure of glaucoma filtration surgery is a scarring response of TF, influenced by growth factors, such as transforming growth factor–ß (TGF–ß). TSP–1 is an extracellular matrix protein, belonging to the group of matricellular proteins and is a potent endogenous activator of extracellular TGF–ß. The activation of TGF–ß by TSP–1 is inhibited by a specific peptide (LSKL) in vitro. CTGF is a secreted peptide that is involved in cell proliferation and fibrosis, and a downstream mediator of TGF–ß. Methods: Expression of TSP–1 and CTGF was assessed by western and northern blotting from cultured human TF after incubation with TGF–ß and dexamethasone. In addition, WST–1 cell proliferation assays were performed after incubation with latent TGF–ß1, dexamethasone and the TSP–1 inhibiting LSKL–peptide. Results: In cultured human TF expression of TSP–1 and CTGF was observed on the protein and mRNA level. After incubation with dexamethasone, activated TGF–ß1 and ß2 a marked increase of mRNA for CTGF and TSP–1 expression was detected. Dexamethasone as well as latent TGF–ß1 markedly increased proliferation of human TF. Incubation with latent TGF–ß1 and the TSP–1 inhibiting LSKL–Peptide significantly reduced cell proliferation of human TF compared to controls without treatment. Conclusions: Incubations of human TF with TGF–ß and dexamethasone promote cell proliferation and induce the expression of TSP–1 and CTGF. Proliferation of human TF was reduced by adding the TSP–1 inhibiting LSKL–peptide. Therefore the LSKL–Peptide could be a helpful tool to reduce scarring response in vivo.
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