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H. Ahn, J. Choi, S. Park, C.–K. Joo; Transforming Growth Factor–ß Induces Expression of the Zinc–Finger Transcription Factor Slug in Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2877.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Epithelial–mesenchymal transition (EMT) is an essential morphogenic process during embryogenesis, but also occurs pathologically. The Snail superfamily of zinc–finger transcription factors is involved in this process through transcriptional repression of E–cadherin production. We investigated whether the Snail family members are involved in EMT of lens epithelial cells via the action of transforming growth factor ß (TGF–ß) and determined the mechanisms by which TGF–ß regulates the expression of the gene family members in lens epithelial cells. Methods: The clinical samples were obtained from patients with anterior polar (AP) or nuclear (NU) cataracts. The human lens epithelial B3 (HLE B3) cells and rat lens epithelial explants were cultured in MEM supplemented with 20% FCS and Medium 199 with 0.1% BSA, respectively. The expression level of Snail and Slug was detected by the real–time RT–PCR and immunoblotting analysis. A siRNA was used to block the expression of Slug. Results: Slug mRNA and protein levels, but not Snail, were highly increased in clinical samples from patients with anterior polar cataracts. Slug levels were increased in both lens and other epithelial cells by TGF–ß, but not in fibroblasts. Transient transfection of Slug cDNA in human lens epithelial B3 (HLE B3) cells resulted in the repression of E–cadherin production, mimicking the initial step of TGF–ß–induced EMT. In addition, the TGF–ß–mediated repression of E–cadherin was significantly inhibited by Slug silencing (si)RNA, indicating that TGF–ß represses the transcription of E–cadherin through the induction of Slug. The Sp1 binding site in the Slug promoter is responsible for TGF–ß–induced Slug expression, and ERK1/2 and JNK pathways are involved in the regulation of Slug by TGF–ß. Conclusions: These data suggest a mechanism by which TGF–ß induces Slug expression, and suggest that Slug might play an important role in the EMT of lens epithelial cells and the formation of anterior polar cataracts.
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