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Avani Mody, Abbot F Clark, Robert J Wordinger, ; BMP4 induced ID proteins protect TM from glaucomatous effects of TGFβ2. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3297.
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Elevated levels of the pro-fibrotic growth factor transforming growth factor β2 (TGFβ2) have been reported in the aqueous humor and trabecular meshwork (TM) of primary open angle glaucoma patients. TGFβ2 treatment results in accumulation of extracellular matrix (ECM) molecules in the TM, which are associated with increased outflow resistance. Expression of TGFβ2 in rodent eyes and ex-vivo anterior segment perfusion models elevate intraocular pressure, suggesting that TGFβ2 plays a role in progression of glaucoma. Interestingly, bone morphogenetic protein 4 (BMP4) in TM inhibits ECM proteins that are up regulated by TGFβ2. The purpose of our study is to determine the mechanism by which BMP4 inhibits the TGFβ2 induction of ECM proteins in the TM. One prominent downstream target of the BMP4 pathway is inhibitor of DNA binding protein (IDs). There are four family members of IDs (ID1-4). In this study, we determine the expression of IDs in TM cells and determine the role of BMP4 induced ID1 and ID3 in regulating TGFβ2 induction of ECM proteins
Time and dose dependent BMP4 induction of ID1 and ID3 were studied in cultured human TM cells by Q-PCR and western blot analysis. GTM3 cells were transfected with pCMV-ID1 and pCMV-ID3 plasmids to determine their effect on TGFβ2 induced ECM proteins (Fibronectin, PAI-1) by western blot analysis.
BMP4 (10ng/ml) significantly induced ID1 and ID3 mRNA and protein expression, starting 30 minutes after treatment (p<0.05). In addition, expression of ID1 and ID3 significantly suppressed the TGFβ2 induction of fibronectin and PAI-1 in TM cells (p<0.05).
BMP4 induced ID1 and ID3 expression in TM cells, and ID1/ID3 suppressed the profibrotic ECM effects of TGFβ2. Therefore, the BMP4 suppression of TGFβ2 effects in TM cells may be mediated by ID1 and ID3.
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