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Bone morphogenetic protein-7 is an antagonist of transforming growth factor-beta2 in human trabecular meshwork cells.

Abstract：

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.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Fuchshofer R,Yu AH,Welge-Lüssen U,Tamm ER

doi

10.1167/iovs.06-0226

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

715-26

issue

eissn

0146-0404

issn

1552-5783

pii

48/2/715

journal_volume

pub_type

杂志文章

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Bone morphogenetic protein-7 is an antagonist of transforming growth factor-beta2 in human trabecular meshwork cells.