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Daisy Yao Shu, Frank J Lovicu; Bone morphogenetic protein (BMP)-7 modulates TGFβ-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells in a dose-dependent manner. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2018. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathological mechanism underlying anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO). Two members of the transforming growth factor-beta (TGFβ) superfamily, TGFβ and bone morphogenetic protein (BMP)-7 play significant but functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, recent studies have shown that BMP-7 can counteract the fibrogenic activity of TGFβ. The present study examines the modulating effect of BMP-7 on TGFβ-induced EMT in LECs.
Lens epithelial explants from 21-day-old Wistar rats were treated with TGFβ2 (200 pg/ml) alone or in combination with different doses of BMP-7 (1, 5, 10, 50ng/ml) for 48 hours. Expression levels of E-cadherin, alpha-smooth muscle actin (α-SMA) and phosphorylated downstream TGFβ signalling molecules, including extracellular-signal-regulated kinase (ERK) 1/2 were determined using immunofluorescence and western blotting. Cell morphology was examined using phase-contrast microscopy.
TGFβ2 induced LECs to elongate and transdifferentiate into myofibroblastic cells positive for α-SMA, with concomitant reduction in E-cadherin. Co-treatment with TGFβ2 and BMP-7 impacted on this transdifferentiation response in a dose-dependent manner. The lowest dose of BMP-7 (1ng/ml) showed no noticeable difference to the TGFβ-alone treated explants while intermediate doses of BMP-7 (5 and 10ng/ml) reduced levels of α-SMA with retention of E-cadherin expression. A higher dose of BMP-7 (50ng/ml) did not impact on the TGFβ-induced transdifferentiation response, with similar levels of α-SMA expression to TGFβ-alone treated explants. Interestingly, this high dose of BMP-7 (50ng/ml) was accompanied by elevated levels of phosphorylated ERK1/2 compared to control and other TGFβ-treated explants.
Treatment with BMP-7 can abrogate TGFβ-induced EMT in rat lens epithelial explants in a dose-dependent manner. Understanding the complex interplay between TGFβ and BMP-7 signalling pathways may hold therapeutic promise in the prevention of ASC and PCO.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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