CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response

Peter Huebener, Tareq Abou-Khamis, Pawel Zymek, Marcin Bujak, Xia Ying, Khaled Chatila, Sandra Haudek, Geeta Thakker, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Infarct healing is dependent on an inflammatory reaction that results in leukocyte infiltration and clearance of the wound from dead cells and matrix debris. However, optimal infarct healing requires timely activation of "stop signals" that suppress inflammatory mediator synthesis and mediate resolution of the inflammatory infiltrate, promoting formation of a scar. A growing body of evidence suggests that interactions involving the transmembrane receptor CD44 may play an important role in resolution of inflammation and migration of fibroblasts in injured tissues. We examined the role of CD44 signaling in infarct healing and cardiac remodeling using a mouse model of reperfused infarction. CD44 expression was markedly induced in the infarcted myocardium and was localized on infiltrating leukocytes, wound myofibroblasts, and vascular cells. In comparison with wild-type mice, CD44 -/- animals showed enhanced and prolonged neutrophil and macrophage infiltration and increased expression of proinflammatory cytokines following myocardial infarction. In CD44null infarcts, the enhanced inflammatory phase was followed by decreased fibroblast infiltration, reduced collagen deposition, and diminished proliferative activity. Isolated CD44 null cardiac fibroblasts had reduced proliferation upon stimulation with serum and decreased collagen synthesis in response to TGF-β4 in comparison to wild-type fibroblasts. The healing defects in CD44-/- mice were associated with enhanced dilative remodeling of the infarcted ventricle, without affecting the size of the infarct. Our findings suggest that CD44-mediated interactions are critically involved in infarct healing. CD44 signaling is important for resolution of the postinfarction inflammatory reaction and regulates fibroblast function.

Original languageEnglish (US)
Pages (from-to)2625-2633
Number of pages9
JournalJournal of Immunology
Volume180
Issue number4
DOIs
StatePublished - Feb 15 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Huebener, P., Abou-Khamis, T., Zymek, P., Bujak, M., Ying, X., Chatila, K., Haudek, S., Thakker, G., & Frangogiannis, N. G. (2008). CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. Journal of Immunology, 180(4), 2625-2633. https://doi.org/10.4049/jimmunol.180.4.2625