Document Detail


Involvement of stem cell factor and c-kit in corneal wound healing in mice.
MedLine Citation:
PMID:  22736941     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To study the roles played by stem cell factor (SCF) and SCF receptor c-kit in wound healing of corneal epithelial cells.
METHODS: A 2 mm corneal epithelial wound was made in control (WBB6F1(+/+)), SCF (Sl/Sl(d))-, and c-kit (W/W(v)) mutant mice, and the speed of wound healing, 5-bromo-2'-deoxyuridine (BrdU) incorporation, and scanning electron microscopic (SEM) morphology of the corneas were examined. The incorporation of BrdU and the degree of cell attachment in cultured mouse corneal epithelial cells (MCECs) isolated from WBB6F1(+/+), Sl/Sl(d), and W/W(v) mice were examined. Cultured immortalized human corneal epithelial cells (HCECs) were examined by a cell attachment assay after their exposure to anti-SCF antibodies, tyrosine kinase inhibitor (genistein), and competitive Arg-Gly-Asp (RGD) peptide, as well as on cultures treated with extracellular matrix.
RESULTS: The speed of corneal wound healing was slower in Sl/Sl(d) and W/W(v) mice than in controls (p<0.01) and the speed of healing in Sl/Sl(d) mice recovered after topical application of SCF (8 ng/ml). No significant difference was found in the BrdU incorporation assay either in vivo or in vitro. Loosened epithelial cells were detected at wound margins in W/W(v) mice by SEM. The cell attachment rate was increased by 157% in cells from WBB6F1(+/+) and 252% in Sl/Sl(d) MCECs by recombinant mouse SCF; however, no significant difference was found in W/W(v) MCECs. Anti-SCF antibodies (Ab), genistein, and RGD peptide reduced the percentage of attached HCECs. Anti-SCF Ab inhibited the attachment of HCECs on fibronectin, laminin, or type IV collagen coated dishes.
CONCLUSIONS: These findings indicate that the SCF/c-kit system may play a role in corneal wound healing through epithelial cell attachment.
Authors:
Kazuhisa Miyamoto; Takeshi Kobayashi; Yasuhito Hayashi; Yuan Zhang; Yuko Hara; Masakatsu Higashine; Atsushi Shiraishi; Yuichi Ohashi
Publication Detail:
Type:  Journal Article     Date:  2012-06-07
Journal Detail:
Title:  Molecular vision     Volume:  18     ISSN:  1090-0535     ISO Abbreviation:  Mol. Vis.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-27     Completed Date:  2012-11-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9605351     Medline TA:  Mol Vis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1505-15     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / pharmacology
Bromodeoxyuridine
Cell Adhesion / drug effects
Collagen Type IV / chemistry
Epithelial Cells / drug effects*,  metabolism,  pathology
Epithelium, Corneal / drug effects*,  metabolism,  pathology
Fibronectins / chemistry
Genistein / pharmacology
Laminin / chemistry
Mice
Mice, Transgenic
Microscopy, Electron, Scanning
Oligopeptides / pharmacology
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-kit / metabolism*
Stem Cell Factor / antagonists & inhibitors,  metabolism,  pharmacology*
Wound Healing / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Antibodies; 0/Collagen Type IV; 0/Fibronectins; 0/Laminin; 0/Oligopeptides; 0/Protein Kinase Inhibitors; 0/Stem Cell Factor; 446-72-0/Genistein; 59-14-3/Bromodeoxyuridine; 99896-85-2/arginyl-glycyl-aspartic acid; EC 2.7.10.1/Proto-Oncogene Proteins c-kit
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