July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Transcription factor SP1 mediates fibrosis as a downstream target of ZEB1 induced by FGF2 in human corneal endothelium
Author Affiliations & Notes
  • Eric Jung
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • JeongGoo Lee
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • J. Martin Heur
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Eric Jung, None; JeongGoo Lee, None; J. Heur, None
  • Footnotes
    Support  NIH EY021485, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1364. doi:
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    • Get Citation

      Eric Jung, JeongGoo Lee, J. Martin Heur; Transcription factor SP1 mediates fibrosis as a downstream target of ZEB1 induced by FGF2 in human corneal endothelium. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1364.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : FGF2 induces endothelial-mesenchymal transition (EnMT) in human corneal endothelium ex vivo, leading to cell proliferation and fibrosis. ZEB1 plays a key role in regulation of EnMT in the corneal endothelium mediated through FGF2. Identification of putative transcriptional activator binding sites in the promoter region of EnMT-realted genes lead us to investigate the role of SP1 in regulating of Col1a1, Col1a2, Fibronectin, and Vimentin expression in ex vivo human corneal endothelium treated with FGF2.

Methods : Human corneas ex vivo were cut into four equal sections and maintained in OptiMEM-1 culture medium with FGF2 for 7 days (n=4 per group). The control group was maintained in culture medium with no FGF2. Accell SMARTpool siRNA targeting ZEB1 and SP1 were used for gene knockdown. The endothelium was isolated from ex vivo corneas, and RNA and protein levels were assessed using RT-PCR and immunoblotting, respectively.

Results : FGF2 stimulation increased SP1 expression in ex vivo human corneal endothelium, which was inhibited by ZEB1 siRNA knockdown. ZEB1 expression was not affected by SP1 siRNA knockdown. However, FGF2-induced expression of fibrosis-related genes, including Fibronectin, Vimentin, Col1a1, and Col1a2, were significantly reduced by SP1 knockdown.

Conclusions : The induction of SP1 by FGF2 through ZEB1 promotes EnMT in human corneal endothelium ex vivo through expression of Fibronectin, Vimentin, Col1a1, and Col1a2.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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