April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Vimentin as a Novel Target of HSF4 in Lens Development and Cataract
Author Affiliations & Notes
  • L. Mou
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
  • J.-Y. Xu
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
    Lab of Clinical Visual Sciences of Tongji Eye Institute and Dept. of Regenerative medicine, Tongji University School of Medicine, Shanghai, China
  • X. Lei
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
  • G.-X. Xu
    Dept. of Ophthalmology, Second Affiliated Hospital of Suzhou University, Suzhou, China
  • Y. Wu
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
  • X. Kong
    Laboratory of Molecular Genetics,
    Institute of Health Sciences, Shanghai, China
  • W. Li
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
    Dept. of Ophthalmology, Drexel University College of Medicine, Philadelphia, Pennsylvania
  • G.-T. Xu
    Lab of Clinical Visual Sciences,
    Institute of Health Sciences, Shanghai, China
    Lab of Clinical Visual Sciences of Tongji Eye Institute and Dept. of Regenerative medicine, Tongji University School of Medicine, Shanghai, China
  • Footnotes
    Commercial Relationships  L. Mou, None; J.-Y. Xu, None; X. Lei, None; G.-X. Xu, None; Y. Wu, None; X. Kong, None; W. Li, None; G.-T. Xu, None.
  • Footnotes
    Support  Translational Research Seeds Fund of the Institute of Health Sciences, Shanghai Institutes for Biological Scineces, Chinese Academy of Sciences
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2114. doi:
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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)

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Abstract

Purpose: : By using the Hsf4 knockout mice (Hsf4-/-) to explore the target genes of HSF4, especially those involved in lens developmental processes and cataract formation.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: cataract • cytoskeleton • proteomics 
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