Adv Wound Care (New Rochelle) 3(12): 762-783

Integrins in Wound Healing

^{Laboratory of Periodontal Biology, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada.}

^{Department of Biochemistry, University of Turku, Turku, Finland.}

^{Correspondence: Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia,, 2199 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada (e-mail:}ac.cbu.yrtsitned@avajral).

Received 2013 Mar 15

Abstract

Significance: Regulation of cell adhesions during tissue repair is fundamentally important for cell migration, proliferation, and protein production. All cells interact with extracellular matrix proteins with cell surface integrin receptors that convey signals from the environment into the nucleus, regulating gene expression and cell behavior. Integrins also interact with a variety of other proteins, such as growth factors, their receptors, and proteolytic enzymes. Re-epithelialization and granulation tissue formation are crucially dependent on the temporospatial function of multiple integrins. This review explains how integrins function in wound repair.

Recent Advances: Certain integrins can activate latent transforming growth factor beta-1 (TGF-β1) that modulates wound inflammation and granulation tissue formation. Dysregulation of TGF-β1 function is associated with scarring and fibrotic disorders. Therefore, these integrins represent targets for therapeutic intervention in fibrosis.

Critical Issues: Integrins have multifaceted functions and extensive crosstalk with other cell surface receptors and molecules. Moreover, in aberrant healing, integrins may assume different functions, further increasing the complexity of their functionality. Discovering and understanding the role that integrins play in wound healing provides an opportunity to identify the mechanisms for medical conditions, such as excessive scarring, chronic wounds, and even cancer.

Future Directions: Integrin functions in acute and chronic wounds should be further addressed in models better mimicking human wounds. Application of any products in acute or chronic wounds will potentially alter integrin functions that need to be carefully considered in the design.

Abstract

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Hannu Larjava, DDS, PhD, Dip. Perio.

Take-Home Messages

Abbreviations and Acronyms

αSMA	alpha–smooth muscle actin
ADAM	a disintegrin and metalloproteinase
BM	basement membrane
CCN	Cyr61-CTGF-Nov
COL	collagen
CT	connective tissue
CTGF	connective tissue growth factor
EC	endothelial cell
ECM	extracellular matrix
EDA/B	extra domain A/B
EGF	epidermal growth factor
EGFR	EGF receptor
EMILIN	elastic microfibril interface–located protein
FAK	focal adhesion kinase
FAP	fibroblast activating protein
FBL	fibroblast
FC	wound (fibrin) clot
FGF	fibroblast growth factor
FN	fibronectin
GT	granulation tissue
HB-EGF	heparin-binding EGF-like growth factor
ICAM	intercellular adhesion molecule
ILK	integrin-linked kinase
KC	keratinocyte
LAP	latency-associated peptide
LM	laminin
LTBP	latent TGF-β1–binding protein
MMP	matrix metalloproteinase
NK	natural killer cell
OPN	osteopontin
PDGF	platelet-derived growth factor
RGD	arginine-glycine-aspartic acid
ROS	reactive oxygen species
SPARC	secreted protein acidic and rich in cysteine
TGF	transforming growth factor
TN	tenascin
TSP	thrombospondin
uPAR	urokinase-type plasminogen activator receptor
VCAM	vascular cell adhesion molecule
VEGF	vascular endothelial growth factor
VN	vitronectin
VWF	von Willebrand factor

Abbreviations and Acronyms

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