Abstract | PURPOSE: To study the role played by HB-EGF in corneal epithelial wound healing. METHODS: A 2-mm corneal epithelial wound was created in keratinocyte-specific, HB-EGF-deficient mice--HB(lox/lox):K-5Cre (HB(-/-))--and the speed of wound healing was compared with that in wild-type (WT) mice. Cultured confluent mouse corneal epithelial cells (MCECs) from WT and HB(-/-) mice were scraped, and the bare area was measured. The proliferation of MCECs was determined by BrdU incorporation. The degree of attachment of WT and HB(-/-) MCECs was also determined. The mRNA expression of EGF family and cell adhesion molecules was determined by real-time PCR. RESULTS: Corneal epithelial wound healing was significantly delayed in HB(-/-) mice, and the expression of HB-EGF was detected at the leading edge of the wound in HB(lox/+):K5-Cre (HB(+/-)) mice by the presence of lacZ staining. The wound closure was significantly impaired in HB(-/-) MCECs and was improved by adding HB-EGF. The number of BrdU-positive MCECs of WT and HB(-/-) mice was not significantly different, and both increased to different degrees when HB-EGF was added. The adhesion of isolated HB(-/-) MCECs was lower than that of WT MCECs, but the degree of adhesion was restored by adding HB-EGF. The expression of epiregulin was upregulated in HB(-/-) MCECs, and α6- and β1-integrin were upregulated by adding HB-EGF. CONCLUSIONS:
HB-EGF plays an important role in corneal epithelial cell healing by enhancing cellular attachment and part of cell proliferation.
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Authors | Ryuji Yoshioka, Atsushi Shiraishi, Takeshi Kobayashi, Shin-Ichi Morita, Yasuhito Hayashi, Shigeki Higashiyama, Yuichi Ohashi |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 51
Issue 11
Pg. 5630-9
(Nov 2010)
ISSN: 1552-5783 [Electronic] United States |
PMID | 20554614
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules
- Hbegf protein, mouse
- Heparin-binding EGF-like Growth Factor
- Intercellular Signaling Peptides and Proteins
- RNA, Messenger
- Epidermal Growth Factor
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Topics |
- Animals
- Cell Adhesion Molecules
(genetics)
- Cell Proliferation
- Cells, Cultured
- Epidermal Growth Factor
(genetics)
- Epithelium, Corneal
(cytology)
- Heparin-binding EGF-like Growth Factor
- Intercellular Signaling Peptides and Proteins
(physiology)
- Keratinocytes
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- RNA, Messenger
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Wound Healing
(physiology)
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