LIGHT -/- mice wounds mimic human chronic ulcers

Melissa L. Petreaca, Danh Do, Sandeep Dhall, Darcie McLelland, Avo Serafino, Julia Lyubovitsky, Neal Schiller, Manuela M. Martins-Green

Research output: Contribution to journalArticle

Abstract

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 (TNFSF14/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/CXCL8, MCP-1/CCL2, IP-10/CXCL10), 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 Coll III, whereas Coll 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.

Original languageEnglish (US)
Pages (from-to)353-366
Number of pages14
JournalWound Repair and Regeneration
Volume20
Issue number3
DOIs
StatePublished - May 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Dermatology

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    Petreaca, M. L., Do, D., Dhall, S., McLelland, D., Serafino, A., Lyubovitsky, J., Schiller, N., & Martins-Green, M. M. (2012). LIGHT -/- mice wounds mimic human chronic ulcers. Wound Repair and Regeneration, 20(3), 353-366. https://doi.org/10.1111/j.1524-475X.2012.00785.x