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Kazuhiko Yoshida, Keiko Nakayama, Hiroyasu Nagahama, Takayuki Harada, Chikako Harada, Junko Imaki, Akira Matsuda, Kazuyuki Yamamoto, Miyuki Ito, Shigeaki Ohno, Kei-Ichi Nakayama; Involvement of p27KIP1 Degradation by Skp2 in the Regulation of Proliferation in Response to Wounding of Corneal Epithelium. Invest. Ophthalmol. Vis. Sci. 2002;43(2):364-370. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To examine the expression of the p27KIP1in the
normal and epithelial-scraped cornea and whether degradation of
p27KIP1by Skp2 is involved in the regulation of cell
proliferation in response to wounding of the corneal epithelium.
methods. C57Bl6, p27KIP1−/−, Skp2−/−, and
Skp2−/−/p27KIP1−/− double-knockout mice
were examined. Normal and epithelial-scraped corneas were analyzed by
immunocytochemistry using anti-p27KIP1 antibody. Cells in
the S phase of DNA synthesis were analyzed by immunocytochemistry using
anti-bromodeoxyuridine (BrdU) antibody.
results. The p27KIP1 was expressed in basal cells of the central and
peripheral region of the cornea and limbus. This expression was not
detected 24 hours after the epithelial scraping, when there were many
cells in the S phase of DNA synthesis in the corneal epithelium. There
were no obvious differences in the thickness and anti-BrdU staining in
the corneal epithelium of p27KIP1−/− mice from that of
control animals. Twenty-four hours after epithelial scraping in the
Skp2−/− mice, the corneal epithelium was thinner than in
wild-type mice and had many p27KIP1-positive cells and few
BrdU-positive cells. In contrast, 24 hours after epithelial scraping in
the Skp2−/−/p27KIP1 −/− double-knockout mice, the corneal epithelium was as thick as in
wild-type mice and had many BrdU-positive cells.
conclusions. These results suggest that degradation of p27KIP1 by Skp2
is involved in the regulation of cell proliferation in response to
wounding of the corneal epithelium.
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