April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Different Cell Proliferation Pathways Induced by FGF-2 Through p27 Degradation via ERK1/2 and PI 3-Kinase in Human and Rabbit Corneal Endothelial Cells
J. Lee; J.-S. Song; R. E. Smith; E. P. Kay
Author Affiliations & Notes
  • J. Lee
    Doheny Eye Institute, Los Angeles, California
  • J.-S. Song
    Doheny Eye Institute, Los Angeles, California
    Ophthalmology, University of Southern California, Los Angeles, California
  • R. E. Smith
    Doheny Eye Institute, Los Angeles, California
    Ophthalmology, University of Southern California, Los Angeles, California
  • E. P. Kay
    Doheny Eye Institute, Los Angeles, California
    Ophthalmology, University of Southern California, Los Angeles, California
  • Footnotes
    Commercial Relationships  J. Lee, None; J.-S. Song, None; R.E. Smith, None; E.P. Kay, None.
  • Footnotes
    Support  NIH Grant EY06431 and EY03040, Research to Prevent Blindness Grant
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2834. doi:
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      J. Lee, J.-S. Song, R. E. Smith, E. P. Kay; Different Cell Proliferation Pathways Induced by FGF-2 Through p27 Degradation via ERK1/2 and PI 3-Kinase in Human and Rabbit Corneal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2834.

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Abstract

Purpose: : To induce cell proliferation, the cyclin-dependent kinase inhibitor p27Kip1 (p27) must undergo proteolysis through its phosphorylation mechanism. FGF-2 stimulates cell proliferation of rabbit corneal endothelial cells (CECs) by degrading p27. We investigated whether to be induced the cell proliferation pathway and p27 degradation by FGF-2 stimulation in human CECs and compared with those of rabbit CECs.

Methods: : Cell proliferation was measured by MTT assay. Expression of ERK1/2, Akt, and FGF-2 was analyzed by immunoblotting. Phosphorylation of Akt, p27, p38 and ERK1/2 was detected by immunoblotting. Intracellular location of p27 and Ki67 was determined by immunofluorescent staining. Pharmacological inhibitors were used to block PI 3-kinase or ERK1/2.

Results: : FGF-2 dramatically stimulated cell proliferation in human CECs; the effects were completely blocked by pathway specific inhibitors for PI 3-knase and ERK1/2, respectively. We further defined whether FGF-2 induces degradation of p27 through its phosphorylation. Cells maintained in serum-starved medium were stained for p27 in the nuclei, but not for pp27Thr187. However, FGF-2 abolished the staining of p27, while nuclear staining of pp27Thr187 was observed. Using immunoblotting we defined that FGF-2 induced phosphorylation of p27 at Ser10 site. The effects of FGF-2 on p27 expression and phosphorylation of p27 at Thr187 site were completely blocked by LY294002 treatment. We used immunoblotting to define whether both PI 3-kinase and ERK1/2 pathways are independently involved in cell proliferation induced by FGF-2, as observed in rabbit CECs. ERK1/2 activation was completely blocked by treatment of PI 3-kinase inhibitor in response to FGF-2 stimulation; ERK1/2 activation involves cell proliferation induced by FGF-2 as a downstream molecule to PI 3-kinase, which differs from rabbit CECs in which the ERK1/2 pathway is parallel to PI 3-kinase pathway.

Conclusions: : FGF-2 stimulates proliferation of human CECs through PI-3 kinase and its downstream target ERK1/2 pathways, and FGF-2 significantly downregulates p27 through the phosphorylation mechanism.

Keywords: cornea: endothelium • cornea: basic science • signal transduction 
© 2010, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
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