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Rudolf Fuchshofer, Marco Birke, Ulrich Welge-Lussen, Daniel Kook, Elke Lütjen-Drecoll; Transforming Growth Factor-β2 Modulated Extracellular Matrix Component Expression in Cultured Human Optic Nerve Head Astrocytes. Invest. Ophthalmol. Vis. Sci. 2005;46(2):568-578. doi: 10.1167/iovs.04-0649.
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purpose. To study whether glaucomatous extracellular matrix (ECM) modifications in the lamina cribrosa might be induced by TGF-β2, the effect of TGF-β2 on the expression of collagen types I (Col1α1), III (Col3α1), and 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 five human donors, and cultured monolayers were treated with 1.0 ng/mL TGF-β2 for 24 and 48 hours. Expression of Col1α1, Col3α1, Col4α2, FN, TGM2, CTGF, and TSP-1 was examined by semiquantitative RT-PCR and Northern and Western blot analyses. The effect of CTGF silencing on the TGF-β2–modulated expression of these genes was investigated by transfection of CTGF small interfering (si)RNA before TGF-β2 treatment.
results. TGF-β2 treatment upregulated the expression of Col1α1, Col4α2, FN, CTGF, TGM2, and TSP-1 mRNA and protein in cultured astrocytes. Inductions ranged between 1.5- and 4-fold. Expression of Col3α1 remained unaffected. Transfection of 10 nM CTGF siRNA inhibited the TGF-β2–induced upregulation of CTGF, Col4α2, Col1α1, TGM2, and FN, whereas TSP-1 expression was not reduced.
conclusions. TGF-β2 is capable of inducing the expression of ECM and basement membrane components in cultured ONH astrocytes via CTGF and upregulated TSP-1, a protein naturally involved in the activation of latent TGF-β. Therefore, TGF-β2 could be a factor in the initiation of the modification of ECM in the glaucomatous ONH. In addition, TSP-1 induction may be a mechanism by which TGF-β2 amplifies its own activation.
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