Adv Wound Care (New Rochelle) 4(4): 213-224

The Roles of Growth Factors in Keratinocyte Migration

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

^{Correspondence: Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Suite 1600, Chicago, IL 60611 (e-mail:}ude.nretsewhtron@rellapa).

Received 2014 Mar 20; Accepted 2014 May 7.

Abstract

Significance: The re-epithelialization of wounded skin requires the rapid and coordinated migration of keratinocytes (KC) into the wound bed. Almost immediately after wounding, cells present at or attracted to the wound site begin to secrete a complex milieu of growth factors. These growth factors exert mitogenic and motogenic effects on KCs, inducing the rapid proliferation and migration of KCs at the wound edge.

Recent Advances: New roles for growth factors in KC biology are currently being discovered and investigated. This review will highlight the growth factors, particularly transforming growth factor-α (TGF-α), heparin-binding epidermal growth factor (HB-EGF), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 7 (FGF-7), FGF-10, and hepatocyte growth factor (HGF), which have conclusively been shown to be the most motogenic for KCs.

Critical Issues: The cellular and molecular heterogeneity of wounded tissue makes establishing direct relationships between specific growth factors and KC migration difficult in situ. The absence of this complexity in simplified in vitro experimental models of migration makes the clinical relevance of the results obtained from these in vitro studies ambiguous.

Future Directions: Deciphering the relationship between growth factors and KC migration is critical for understanding the process of wound healing in normal and disease states. Insights into the basic science of the effects of growth factors on KC migration will hopefully lead to the development of new therapies to treat acute and chronic wounds.

Abstract

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Amy S. Paller, MS, MD

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Abbreviations and Acronyms

ACh	acetylcholine
AGF	angiopoietin-related growth factor
ECM	extracellular matrix
EGF	epidermal growth factor
FB	fibroblast
FGF	fibroblast growth factor
FGFBP	FGF binding proteins
GM-CSF	granulocyte macrophage-colony stimulating factor
HB-EGF	heparin binding-epidermal growth factor
HGF	hepatocyte growth factor
HMGB1	high mobility group protein β1
HP	hepatocytes
HSP90	heat shock protein 90
IGF-1	insulin-like growth factor 1
IGF1R	IGF-1 receptor
IGFBP	IGF binding protein
IL	interleukin
IR	insulin receptor
KC	keratinocyte
LK	leukocyte
MAPK	mitogen-activated protein kinase
ML	melanocytes
MMP	matrix metalloproteinases
MSP	macrophage-stimulating protein
NEP	neutral endopeptidase
NK1R	neurokinin 1 receptor
PB	pancreatic β-cells
PDGF-BB	platelet-derived growth factor BB
PI3K	phosphatidylinositol-3-kinase
PKCδ	protein kinase Cδ
PNS	peripheral nervous system cells
RTK	receptor tyrosine kinases
SOCS3	suppressor of cytokine signaling 3
SP	substance P
STAT3	signal transducer and activator of transcription 3
TGF-α	transforming growth factor-α
TNF-α	tumor necrosis factor-α
VEGF	vascular endothelial growth factor
VEGFR	VEGF RTK receptor
VIP	vasoactive intestinal peptide

Abbreviations and Acronyms

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