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Role of the Receptor CXCR3 and its Ligand in Wound Healing
Author(s) -
Kulasekaran Priya,
Hebda Patricia A.,
Satish Latha,
Yager Dorne,
Hancock Wayne W.,
Lu Bao,
Wells Alan
Publication year - 2008
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.1067-1927.2005.130215r.x
Subject(s) - wound healing , cxcr3 , chemistry , granulation tissue , receptor , extracellular matrix , microbiology and biotechnology , angiogenesis , chemokine , chemokine receptor , biology , immunology , cancer research , biochemistry
We find that the ELR‐negative CXC chemokines, CXCL10 (IP‐10) and CXCL11(IP‐9), expressed during wound repair, with IP‐9 being produced by redifferentiated keratinocyte. Immunohistochemical analysis for IP‐9 on human full thickness wound tissues collected from day 5 confirmed that IP‐9 is a wound response protein. We have shown in in vitro coculture systems that IP‐9 can serve as an autocrine factor promoting motility in keratinocyte while limiting motility in dermal fibroblasts. These effects occur via modulation of the intracellular proteases calpain isoforms that regulate cell adhesion during motility. Thus, the function of these chemokines in vivo is not obvious. To probe this, we have explored wound repair in mice lacking the receptor for these ligands, CXCR3. Quantitative analysis of IP‐9 expression in wounds of these mice collected from day 2 to day 20 showed a significant increase in IP‐9 levels in CXCR3‐/‐ mice compared to wild type, which is expected if receptor‐mediated feedback attenuation is lost. Full and partial thickness wound healing experiments on these mice showed a significant delay in CXCR3‐/‐ mice when compared to wild type. Histochemical analysis of tissues collected from both full and partial thickness wounds demonstrated differences in epithelialization, granulation tissue formation, and angiogenesis in CXCR3‐/‐ mice when compared to wild type. Collagen, the major extracellular matrix protein organization were analyzed by trichrome and picrosirus red staining methods. We are also examining the effect of this lost receptor on promotility signaling from EGF receptors. These in vivo and in vitro studies confirm the pathophysiologic role of the chemokines IP‐9 and IP‐10 and their cognate receptor CXCR3 during wound repair.