title: Chronic wounds - is cellular 'reception' at fault? Examining integrins and intracellular signalling.
abstract: As with all physiologic processes, chronic wounds are associated with unique intracellular and cellular/extracellular matrix (ECM) receptor types and signalling messages. These cellular receptors mediate responses of the epidermis to provisional wound matrix and change in form and number in cases of impaired wound healing. Integrins are the major cell-surface receptors for cell adhesion and migration and epidermal keratinocytes express several integrins that bind ECM ligands in provisional wound ECM. Integrin receptors and more particularly integrin clusters and focal adhesion points appear to influence epidermal and dermal cell matrix interactions, cell motility, cell phenotype and ultimate healing trajectory. In chronic wounds, a variety of changes in receptors have been identified: decreased integrin α5β1 receptors affect the integration of fibronectin and subsequent keratinocyte migration; integrin αvβ6 stimulate transforming growth factor (TGF)-β and may increase the susceptibility to ulceration and fibrosis; however, TGF-β signal receptors have been found to be dysfunctional in many chronic wounds; additionally receptor interactions result in increased senescent cells including fibroblasts, myofibroblasts and even keratinocytes - this produces a degradative ECM and wound bed and corrosive chronic wound fluid. The activation or inhibition of integrin receptors by various agents may provide an excellent means of influencing wound healing. This process offers an earlier intervention into the wound healing cascade promoting intrinsic healing and elaboration of growth factors and ECM proteins, which may be more cost effective than the traditional attempts at extrinsic addition of these agents.
authors.affiliation: Faculty of Health Sciences, Plastic Surgery Department, University of the Witwatersrand, Johannnesburg, South Africa and Adar science Inc., Irvine, CA, USA. awidgerow@adarscience.com
authors.forename: Alan D
authors.initials: AD
authors.lastname: Widgerow
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016023:Integrins; D011956:Receptors, Cell Surface