Bone Morphogenetic Protein-7 Is an Antagonist of Transforming Growth Factor-{beta}2 in Human Trabecular Meshwork Cells.
PURPOSE: The increase in intraocular pressure in primary open-angle glaucoma (POAG) may involve transforming growth factor (TGF)-beta2 signaling, as TGF-beta2 is found in higher amounts than normal in the aqueous humor of patients with POAG. In vitro, TGF-beta2 causes an accumulation of extracellular matrix ( ECM) in the trabecular meshwork (TM) and an increase in TM outflow resistance. The present study was undertaken to determine whether bone morphogenetic protein (BMP)-7 signaling antagonizes the effects of TGF-beta2 on TM cells. METHODS: Cultured TM cells from nine human donors were treated with BMP-7, TGF-beta2, or a combination of both for 24 or 72 hours. The expression of connective tissue growth factor (CTGF); thrombospondin (TSP)-1; fibronectin; collagen types I, III, and IV; plasminogen activator inhibitor (PAI)-1; and matrix metalloproteinase (MMP)-2 were analyzed by immunohistochemistry, real time RT-PCR, Western and Northern blot analysis, and zymography (MMP-2). RESULTS: Treatment with TGF-beta2 induced the expression of CTGF, TSP-1, fibronectin, collagen types IV and VI, and PAI-1. All these effects were inhibited when TGF-beta2 was added in combination with BMP-7, whereas BMP-7 alone had no effects. Treatment with TGF-beta2, BMP-7, or the combination of both had no effect on the expression of collagen types I and III. CONCLUSIONS: BMP-7 strongly antagonizes in vitro the TGF-beta-induced expression of a broad panel of molecules, which would result in an accumulation of TM ECM in situ. As BMP-7 is expressed in the adult human TM in situ, it seems reasonable to assume that it similarly modulates and antagonizes the effects of TGF-beta2 signaling on the tissues of the outflow pathways in vivo. The pharmacological modulation of BMP-7 signaling in the TM might be a promising strategy to treat POAG.[1]References
- Bone Morphogenetic Protein-7 Is an Antagonist of Transforming Growth Factor-{beta}2 in Human Trabecular Meshwork Cells. Fuchshofer, R., Yu, A.H., Welge-Lüssen, U., Tamm, E.R. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
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