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2016 ; 365
(3
): 467-82
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Integrin-mediated regulation of epidermal wound functions
#MMPMID27351421
DiPersio CM
; Zheng R
; Kenney J
; Van De Water L
Cell Tissue Res
2016[Sep]; 365
(3
): 467-82
PMID27351421
show ga
During cutaneous wound healing, keratinocyte proliferation and migration are
critical for re-epithelialization. In addition the epidermis secretes growth
factors, cytokines, proteases, and matricellular proteins into the wound
microenvironment that modify the extracellular matrix and stimulate other wound
cells that control the inflammatory response, promote angiogenesis and facilitate
tissue contraction and remodeling. Wound keratinocytes express at least seven
different integrins-the major cell adhesion receptors for the extracellular
matrix-that collectively control essential cell-autonomous functions to ensure
proper re-epithelialization, including migration, proliferation, survival and
basement membrane assembly. Moreover, it has become evident in recent years that
some integrins can regulate paracrine signals from wound epidermis that stimulate
other wound cells involved in angiogenesis, contraction and inflammation.
Importantly, it is likely that abnormal integrin expression or function in the
epidermis contributes to wound pathologies such as over-exuberant healing (e.g.,
hypertrophic scar formation) or diminished healing (e.g., chronic wounds). In
this review, we discuss current knowledge of integrin function in the epidermis,
which implicates them as attractive therapeutic targets to promote wound healing
or treat wound pathologies. We also discuss challenges that arise from the
complex roles that multiple integrins play in wound epidermis, which may be
regulated through extracellular matrix remodeling that determines ligand
availability. Indeed, understanding how different integrin functions are
temporally coordinated in wound epidermis and which integrin functions go awry in
pathological wounds, will be important to determine how best to target them
clinically to achieve maximum therapeutic benefit. Graphical abstract In addition
to their well-characterized roles in keratinocyte adhesion, migration and wound
re-epithelialization, epidermal integrins play important roles in modifying the
wound microenvironment by regulating the expression and secretion of growth
factors, extracellular proteases, and matricellular proteins that stimulate other
wound cells, including vascular endothelial cells and fibroblasts/myofibroblasts.
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