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M. Birke, R. Fuchshofer, U. Welge–Lüssen, D. Kook, E. Lutjen–Drecoll; Transforming Growth Factor (TGF)–ß2 Modulated Extra–Cellular Matrix Component Expression in Cultured Human Optic Nerve Head Astrocytes . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1273.
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Purpose: To study if glaucomatous extracellular matrix (ECM) modifications in the lamina cribrosa might be induced by TGF–ß2, the effect of TGF–ß2 on the expression of collagen type I (Col1α1), III (Col3α1), IV (Col4α2), fibronectin (FN), tissue transglutaminase(TGM2), connective tissue growth factor (CTGF) and thrombospondin (TSP–1) in cultured human optic nerve head (ONH)astrocytes was investigated. Methods: Astrocytes were isolated from eyes of 5 human donors and cultured monolayers were treated with 1.0 ng/ml TGF–ß2 for 24 and 48h.Expression of Col1α1, Col3α1, Col4α2, FN, TGM2, CTGF and TSP–1 was examined by semiquantitative RT–PCR, northern and western blots. The effect of CTGF silencing on the TGF–ß2 modulated expression of these genes was investigated by transfection of CTGF siRNA prior to TGF–ß2 treatment. Results: TGF–ß2 treatment upregulated the expression of Col1α1, Col4α2, FN, CTGF, TGM2 and TSP–1 mRNA and protein in cultured astrocytes. Fold inductions ranged between factor 1.5 to 4. Expression of Col3α1 remained unaffected. Transfection of 10 nM CTGF siRNA inhibited the TGF–ß2 induced upregulation of CTGF, Col4α2, Col1α1, TGM2 and FN, whereas TSP–1 expression was not reduced. Conclusions: TGF–ß2 is capable of inducing the expression of ECM and basement membrane (BM) components in cultured ONH astrocytes via CTGF and upregulated TSP–1, a protein naturally involved in the activation of latent TGF–ß. Therefore TGF–ß2 could be a factor that might be involved in the initiation of the modifications of ECM in glautcomatous ONH. Additionally, TSP–1 induction might be a mechanism by which TGF–ß2 amplifies its own activation.
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