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Role of epidermal growth factor and epidermal growth factor receptor on hemidesmosome complex formation and integrin subunit β4

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Abstract.

Epidermal growth factor (EGF) stimulates integrin β4 expression and synthesis in corneal epithelium through ligand binding to the EGF receptor, receptor dimerization and activation of the intracellular domain. We hypothesized that inhibition of EGF receptor messenger RNA (mRNA) would block integrin β4 expression, which is induced by EGF. We also tested the hypothesis that EGF would cause the degradation of hemidesmosomes in control and injured corneal organ cultures. Primary rabbit corneal epithelial cell cultures or corneas were cultured in keratinocyte medium in the presence or absence of an antisense 20-mer phosphorothioate oligonucleotide complementary to the initiation codon region of EGF receptor mRNA. Cells were also cultured in the presence or absence of EGF. Sense and scrambled oligonucleotides similarly modified were used as controls. The concentration of EGF receptor mRNA was semiquantitatively determined by reverse transcriptase/polymerase chain reaction (RT-PCR). We found that transfection did inhibit EGFR expression and migration of epithelial cells and also demonstrated that EGFR mediated expression of integrin β4 mRNA. Injury induced a decrease in hemidesmosomes that was enhanced with EGF but was not caused by the presence of growth factor in unwounded tissue. These results indicate that injury causes the activation of EGFR but that EGF alone is not responsible for the degradation of hemidesmosomes and that other growth factors play a role in the complex repair of wounds in an avascular tissue.

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Acknowledgements.

We thank Johanna Payne and Rozanne Richmond for excellent technical assistance and Veronica Klepeis for critical discussions.

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Authors and Affiliations

  1. Departments of Biochemistry and Ophthalmology, Boston University School of Medicine, Boston, MA, 02118, USA

    Q. H. Song, H. Gong & V. Trinkaus-Randall

  2. Boston University School of Medicine, L903, 80 E. Concord Street, Boston, MA, 02118, USA

    V. Trinkaus-Randall

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  1. Q. H. Song
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  2. H. Gong
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Correspondence to V. Trinkaus-Randall.

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This work was supported by NEI grant EY06000 (V.T.-R.) and by departmental grants from the Massachusetts Lions Eye Research Fund, Research to Prevent Blindness, Inc., and the New England Corneal Transplant Fund

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Song, Q.H., Gong, H. & Trinkaus-Randall, V. Role of epidermal growth factor and epidermal growth factor receptor on hemidesmosome complex formation and integrin subunit β4. Cell Tissue Res 312, 203–220 (2003). https://doi.org/10.1007/s00441-002-0693-x

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