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Z. Wang, C.–Y. Liu, H. Yang, V. Bildin, P. Reinach; Dependence of EGF–Induced Increases in Corneal Epithelial Migration on Extent of Crosstalk Between P38 and P44/42 Mapk Limbs . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2608.
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© ARVO (1962-2015); The Authors (2016-present)
In many different cell types, cytokines increase epithelial cell migration through activation of the p38 limb of the MAPK superfamily. Such a response is essential to hasten wound healing subsequent to corneal epithelial injury. Accordingly, we determined in three different SV40–immortalized rabbit corneal epithelial cell (RCEC) lines if there is an association between growth factor induced p38 stimulation and increases in cell migration.
RCEC and two different tetracycline inducible d/n MAPK stably transfected RCEC lines were used to modulate epidermal growth factor, EGF stimulation of p38 MAPK activity and migration: 1) Erk1(d/n); 2) p38(d/n). Kinases activation was monitored with Western blot/ECL analysis. Growth factor (i.e. 10% FBS) dependent effects on cell migration were measured with the Transwell assay.
In RCEC, 10 ng/ml EGF induced a 20–fold increase in Erk1 activity after 5 min and a 3.5–fold increase in p38 activity after 30 min. Inhibition of EGF–induced activation of Erk1/2 by 10 µM PD98059 led to a 35% increase in p38 phosphorylation. On the other hand, inhibition of p38 activation with 20 µM SB203580 increased Erk1/2 activation up to 2.5–fold. Inhibition of p38 nearly completely inhibited cell migration. Induction of d/n p38 expression caused 2–fold increase in EGF–mediated Erk1/2 activation. Activation of Erk1(d/n) expression maximally increased EGF–induced p38 phosphorylation by 2.5–fold, which occurred already after 5 min rather than after 15 min in the absence of tetracycline. This augmented EGF–induced p38 activation was associated with a 40% increase in cell migration over that measured in Erk1(d/n) cells in the absence of tetracycline.
There is a correspondence between the magnitude of EGF–induced p38 activation and cell migration. Suppression of ERK limb activity maximally stimulated cell migration such an effect is evidence for crosstalk between the ERK and p38 cascades in mediating control of cell migration.
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