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Ashley F. Taylor, Abbot F. Clark, Robert J. Wordinger; Characterization of Follistatin and Associated Molecules in Human Trabecular Meshwork Cells and Tissues. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4643.
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© ARVO (1962-2015); The Authors (2016-present)
Elevated intraocular pressure from increased resistance of aqueous humor (AH) outflow through the trabecular meshwork (TM) is a major risk factor in glaucoma. TGF-ß2 is increased in the AH and TM of glaucoma patients, and increases extracellular matrix (ECM) deposition. We have reported that BMP-4 attenuates TGF-β2 induced ECM deposition, and BMP antagonist gremlin blocks this inhibitory effect. Follistatin (FST), another BMP antagonist, regulates TGF-ß signaling via interaction with activins (Act) and BMPs. Three isoforms of FST (288, 315, 303) have been reported. Microarray studies have also identified FST-like (FST-L) protein expression in human TM (HTM) cells. The purpose of this study was to: (a) further characterize FST isoform expression in TM cells and tissues, (b) determine if HTM cells and tissues express FST-L proteins and Act and (c) determine if exogenous TGF- ß2 regulates their expression.
QRT-PCR was used to determine mRNA expression of FST, Act A, B, C and E, and FST-L1-5 in HTM cell strains (N=5). Western blot and immunohistochemistry were used to demonstrate protein levels in cells and tissues. TM cells were cultured with or without TGF- ß2 (2.5 ng/ml) for 48 hrs.
QRT-PCR demonstrated that FST isoforms were expressed by TM cells. FST was also expressed in normal and glaucomatous TM tissues. mRNA for Act A, B and C as well as Act A and B proteins were expressed by TM cells. FST-L1-3 mRNA and FST-L3 protein was detected in TM cells. TGF-ß2 significantly increased FST (p<0.05), Act A and B including FST-L3 protein in TM cells.
This is the first report of the expression of FST 317/344, Act A&B, and FST-L1-3 mRNA and protein in TM cells and tissues. These results will further our understanding of the regulation of TGF- ß2/BMP signaling pathways in the TM and their possible role in glaucoma.
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