Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2010 Apr;176(4):1743-55. doi: 10.2353/ajpath.2010.090564. Epub 2010 Mar 4.

Lack of CXC chemokine receptor 3 signaling leads to hypertrophic and hypercellular scarring.

Author information

  • 1University of Pittsburgh, Department of Pathology, Pittsburgh, PA 15261, USA.

Abstract

CXC chemokine receptor 3 (CXCR3) signaling promotes keratinocyte migration while terminating fibroblast and endothelial cell immigration into wounds; this signaling also directs epidermal and matrix maturation. Herein, we investigated the long-term effects of failure to activate the "stop-healing" CXCR3 axis. Full-thickness excisional wounds were created on CXCR3 knockout((-/-)) or wild-type mice and examined at up to 180 days after wounding. Grossly, the CXCR3(-/-) mice presented a thick keratinized scar compared with the wild-type mice in which the scar was scarcely noticeable; histological examination revealed thickening of both the epidermis and dermis. The dermis was disorganized with thick and long collagen fibrils and contained excessive collagen content in comparison with the wild-type mice. Interestingly, the CXCR3(-/-) wounds presented lower tensile/burst strength, which correlates with decreased alignment of collagen fibers, similar to published findings of human scars. Persistent Extracellular matrix turnover and immaturity was shown by the elevated expression of proteins of the immature matrix as well as expression of matrix metallopeptidase-9 MMP-9. Interestingly, the scars in the CXCR3(-/-) mice presented evidence of de novo development of a sterile inflammatory response only months after wounding; earlier periods showed resolution of the initial inflammatory stage. These in vivo studies establish that the absence of CXCR3(-/-) signaling network results in hypertrophic and hypercellular scarring characterized by on-going wound regeneration, cellular proliferation, and scars in which immature matrix components are undergoing increased turnover resulting in a chronic inflammatory process.

Comment in

PMID:
20203286
[PubMed - indexed for MEDLINE]
PMCID:
PMC2843466
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk