Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1.

Autor: Kim CS; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA., Mitchell IP; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA., Desotell AW; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA., Kreeger PK; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA kreeger@wisc.edu., Masters KS; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA kmasters@wisc.edu.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2016 Jul; Vol. 30 (7), pp. 2580-90. Date of Electronic Publication: 2016 Mar 29.
DOI: 10.1096/fj.201600252
Abstrakt: Epidermal growth factor (EGF) is a critical element in dermal repair, but EGF-containing wound dressings have not been successful clinically. However, these dressings have delivered only soluble EGF, and the native environment provides both soluble and matrix-bound EGF. To address our hypothesis that tethered EGF can stimulate cell behaviors not achievable with soluble EGF, we examined single-cell movement and signaling in human immortalized HaCaT keratinocytes treated with soluble or immobilized EGF. Although both EGF treatments increased collective sheet displacement and individual cell speed, only cells treated with immobilized EGF exhibited directed migration, as well as 2-fold greater persistence compared with soluble EGF. Immunofluorescence showed altered EGF receptor (EGFR) trafficking, where EGFR remained membrane-localized in the immobilized EGF condition. Cells treated with soluble EGF demonstrated higher phosphorylated ERK1/2, and cells on immobilized EGF exhibited higher pPLCγ1, which was localized at the leading edge. Treatment with U0126 inhibited migration in both conditions, demonstrating that ERK1/2 activity was necessary but not responsible for the observed differences. In contrast, PLCγ1 inhibition with U73122 significantly decreased persistence on immobilized EGF. Combined, these results suggest that immobilized EGF increases collective keratinocyte displacement via an increase in single-cell migration persistence resulting from altered EGFR trafficking and PLCγ1 activation.-Kim, C. S., Mitchell, I. P., Desotell, A. W., Kreeger, P. K., Masters, K. S. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1.
(© FASEB.)
Databáze: MEDLINE
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