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Scarring of dermal wounds in the absence of CXCR3 involves both the dermal and epidermal compartments
Author(s) -
Yates Cecelia Chrsitina,
Krisha Priya,
Whaley Diana,
Bodnar Richard,
Turner Timothy,
Wells Alan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.236.8
Subject(s) - dermis , scars , paracrine signalling , wound healing , hypertrophic scar , myofibroblast , cxcr3 , pathology , microbiology and biotechnology , fibroblast , epidermis (zoology) , fibrosis , skin repair , chemistry , biology , medicine , anatomy , receptor , immunology , chemokine , chemokine receptor , in vitro , biochemistry
Healing of excisional wounds requires coordinated remodeling of two tissue compartments, the ectodermally‐derived epithelial epidermis and the mesodermally‐derived mesenchymal dermis. The cellular effects and timely expression of CXCR3 and its ligands IP‐9 and IP‐10 highlights this signaling system as key to communication between the compartments to end the remodeling phase as persistence of this phase leads to scar formation. In this study we determined the long‐term consequences of failure to activate this receptor and its ligands. The absence of CXCR3 in mice resulted in a visibly hypertrophic scar that was hyalinized, thickened and multidirectional growth of collagen bundles resembling scars of fibroproliferative disease of the skin in humans. Histological assessments confirmed the abnormal healing patterns and revealed a persistent chronic inflammatory response. The CXCR3‐/‐ mice resulted in 50% increase in the content of collagen, lower tensile/burst strength, and a decrease in collagen alignment. Additionally, significantly higher levels of proliferation and apoptosis were observed. Transwells co‐cultures of keratinocytes and fibroblast revealed abnormalities in epidermal‐dermal crosstalk of CXCR3‐/‐ mice. These vivo studies suggest that CXCR3 signaling system acts in a paracrine fashion to modulate epidermal‐dermal maturation with its absence resulting in hypertrophic scarring.