Fig. 2.

CXCR3 signaling axis during wound repair. CXCR3 receptor is a seven transmembrane G protein coupled receptor. This signaling system is extant in human and rodent with the receptor being ubiquitous but the ligands being regulated temporally and spatially. CXCR3 receptor is expressed on keratinocytes, fibroblast, and endothelial cells. CXCL10/IP-10 appears in the dermis and is produced by endothelial cells of the neovasculature and CXCL11/IP-9 is expressed from redifferentiating keratinocytes behind the leading edge of the wound. These secreted peptide factors, both CXC chemokines that lack the canonical N-terminal sequence ELR (glutamic acid-leucine-arginine), bind in common to the ubiquitous CXCR3 chemokine receptor. Signaling through CXCR3 blocks growth factor-induced motility of fibroblasts and endothelial cells by suppressing m-calpain activation. In contrast, these chemokines do not block the motility of dedifferentiated keratinocytes but rather increase their motility via lessened adhesiveness that shifts the cell into the most permissive adhesion/contractility state and thus promotes motility and in turn more rapid re-epithelialization. For endothelial cells, in which the β3 integrin predominates, CXCR3 activation of calpain1/μ-calpain leads to detachment and anoikis