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Deletion of a tumor necrosis superfamily gene in mice leads to impaired healing that mimics chronic wounds in humans
Author(s) -
Petreaca Melissa L.,
Do Danh,
Dhall Sandeep,
McLelland Darcie,
Serafino Avo,
Lyubovitsky Julia,
Schiller Neal,
MartinsGreen Manuela M.
Publication year - 2012
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2012.00785.x
Subject(s) - granulation tissue , chemokine , wound healing , inflammation , tumor necrosis factor alpha , basement membrane , immunology , medicine , angiogenesis , chronic wound , proinflammatory cytokine , pathology , biology , cancer research
Proper healing of cutaneous wounds progresses through a series of overlapping phases. Nonhealing wounds are defective in one or more of these processes and represent a major clinical problem. A critical issue in developing treatments for chronic wounds is the paucity of animal models to study the mechanisms underlying the defects in healing. Here we show that deletion of tumor necrosis factor superfamily member 14 ( TNFSF 14/ LIGHT ) leads to impaired wounds in mice that have the characteristics of nonchronic and chronic ulcers. These wounds show: (1) excessive production of cytokines, in particular three chemokines ( KC / CXCL 8, MCP ‐1/ CCL 2, IP ‐10/ CXCL 10), that may be key to the abnormal initiation and resolution of inflammation; (2) defective basement membranes, explaining blood vessel leakage and disruption of dermal/epidermal interactions; and (3) granulation tissue that contains high levels of C oll III , whereas C oll I is virtually absent and does not form fibrils. We also see major differences between nonchronic and chronic wounds, with the latter populated by bacterial films and producing eotaxin, a chemokine that attracts leukocytes that combat multicellular organisms (which biofilms can be considered to be). This new mouse model captures many defects observed in impaired and chronic human wounds and provides a vehicle to address their underlying cell and molecular mechanisms.