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L. Mou, J.-Y. Xu, X. Lei, G.-X. Xu, Y. Wu, X. Kong, W. Li, G.-T. Xu; Vimentin as a Novel Target of HSF4 in Lens Development and Cataract. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2114.
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© ARVO (1962-2015); The Authors (2016-present)
By using the Hsf4 knockout mice (Hsf4-/-) to explore the target genes of HSF4, especially those involved in lens developmental processes and cataract formation.
Lenses of Hsf4-/- and wild-type (Hsf4+/+) mice were examined under slit-lamp microscopy to assess lens development and cataract formation. Two-dimensional electrophoreses combined with MS/MS were used to identify differentially expressed lens proteins between Hsf4+/+ and Hsf4-/- mice. The differentially expressed gene products were further confirmed by western blot, Q-PCR and immunofluorescence analysis.
Hsf4-/- mice had abnormal lenses and developed cataract. The down-regulated proteins were major structural proteins including crystallins and β crystallins, while the up-regulated proteins were mainly enzymes and an intermediate filament protein, vimentin. The up-regulated vimentin expression level was further confirmed by western bolt, Q-PCR and immunofluorescence. Electrophoretic mobility shift assay validated that HSF4 had DNA-binding ability to vimentin gene.
The present study has identified vimentin as a novel target of HSF4 in lens, and proposed a mechanism by which the mutation of HSF4 leads to abnormal lens development and cataract formation.
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