HaCaT keratinocyte migration is dependent on epidermal growth factor receptor signaling and glycogen synthase kinase-3[alpha]
After epithelial disruption by tissue injury, keratinocytes migrate from the wound edge into a provisional matrix. This process is stimulated by growth factors that signal through epidermal growth factor (EGF) receptor, including EGF, heparin-binding EGF-like growth factor (HB-EGF) and transforming...
Saved in:
Published in | Experimental cell research Vol. 312; no. 15; p. 2791 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Elsevier BV
10.09.2006
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | After epithelial disruption by tissue injury, keratinocytes migrate from the wound edge into a provisional matrix. This process is stimulated by growth factors that signal through epidermal growth factor (EGF) receptor, including EGF, heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor-[alpha] (TGF-[alpha]), and by for example keratinocyte growth factor (KGF) and TGF-[alpha]1 that function through different receptors. We have previously shown that keratinocyte migration induced by EGF or staurosporine is dependent on the activity of glycogen synthase kinase-3 (GSK-3). In the present study, we show that keratinocyte migration induced by TGF-[alpha]1, KGF, EGF, TGF-[alpha] and staurosporine depends on EGFR signaling, involves autocrine HB-EGF expression and is potently blocked by GSK-3 inhibitors SB-415286 and LiCl. Inhibition of GSK-3 also retards wound reepithelialization in vivo in mice. Moreover, inhibition of GSK-3 activity prevented cell rounding that is an early event in EGFR-mediated keratinocyte migration. Isoform-specific GSK-3[alpha] and GSK-3[alpha] knockdown and overexpression experiments with siRNAs and adenoviral constructs, respectively, revealed that GSK-3[alpha] is required for keratinocyte migration, whereas excessive activity of GSK-3[alpha] is inhibitory. Thus, induction of keratinocyte migration is conveyed through EGFR, promoted by endogenous HB-EGF and requires GSK-3[alpha] activity. [PUBLICATION ABSTRACT] |
---|---|
ISSN: | 0014-4827 1090-2422 |
DOI: | 10.1016/j.yexcr.2006.05.009 |