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Arch Dermatol Res. 2009 Apr;301(4):307-17. doi: 10.1007/s00403-009-0945-7. Epub 2009 Mar 28.

Coordinated integrin and growth factor regulation of primary keratinocyte migration mediated through extracellular signal regulated kinase and phosphoinositide 3-kinase.

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1
Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.

Abstract

We have examined coordinated integrin and growth factor regulation of primary keratinocyte migration mediated by phosphoinositide 3-kinase (PI3K) and mitogen-activated extracellular-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK). On collagen I and fibronectin substrates, both epidermal growth factor (EGF) and hepatocyte growth factor (HGF) stimulated chemokinetic (random) and chemotactic (directional) migration. On provisional matrix, a combination of fibronectin and fibrin found in the early phase of wound healing, EGF and HGF-stimulated significant chemotactic but little or no chemokinetic cell movement. Blocking mAbs to integrin alpha2beta1 and alpha5beta1 effectively inhibited EGF- and HGF-stimulated chemokinetic and chemotactic cell movement on collagen I and fibronectin, respectively; however, HGF-stimulated chemotactic migration on collagen I was only partially inhibited by alpha2beta1 blocking mAb. Differentiated keratinocytes underwent reduced chemokinetic and chemotactic migration compared with undifferentiated keratinocytes; however, EGF-stimulated migration was reduced more than HGF-stimulated migration. When the migratory response on collagen I and fibronectin was assessed in the presence of the MEK-specific inhibitor PD98059, EGF- and HGF-stimulated chemotaxis was significantly reduced, whereas PD98059 had little effect on the stimulated chemokinesis. PI3K-specific inhibitor LY294002 reduced EGF- and HGF-stimulated chemokinesis and chemotaxis on collagen I and fibronectin. Thus beta1 integrins acted in concert with EGF and HGF to regulate migration of primary keratinocytes on extracellular matrix components via PI3K and MEK/ERK.

PMID:
19330341
DOI:
10.1007/s00403-009-0945-7
[Indexed for MEDLINE]
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