Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells.
OBJECTIVE
Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells.


METHODS
Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy.


RESULTS
Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair-related genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution.


CONCLUSIONS
Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.
Hafner
Christian
C
Department of Dermatology, University of Regensburg, Regensburg D-93042, Germany.
Meyer
Stefanie
S
Hagen
Ilja
I
Becker
Bernd
B
Roesch
Alexander
A
Landthaler
Michael
M
Vogt
Thomas
T
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D036387:Ephrin-B1 / Q000235:genetics* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D014945:Wound Healing / Q000502:physiology*
D036387:Ephrin-B1