Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo

Istvan Juhasz, George F. Murphy, Horng Chin Yan, Meenhard Herlyn, Steven M. Albelda

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Although changes in extracellular matrix proteins during wound healing have been well documented, little is known about the regulation of corresponding extracellular matrix adhesion receptors (integrins). To study this process in a human in vivo model, full thickness human skin grafts were transplanted onto severe combined immunodeficient mice and deep excisional wounds involving both the epidermal and dermal layers were then made. The changes in the expression of cell matrix proteins and epithelial integrins over time were analyzed with specific antibodies using immunohistochemistry. Wounding was associated with alterations in extracellular matrix proteins, namely, loss of laminin and type IV collagen in the region of the wound and expression of tenascin and fibronectin. Changes were also noted in the integrins on the migrating keratinocytes. There was marked upregulation of the α, subunit and de novo expression of the fibronectin receptor (α5β1) during the stage of active migration (days 1 to 3 after wounding). In the later stages of wound healing, after epithelial integrity had been established, redistribution of the α2, α3, α6, and β4 collagen/laminin-binding integrin subunits to suprabasal epidermal layers was noted. Thus, during cutaneous wound healing, keratinocytes up-regulate fibronectin/fibrinogen-binding integrins and redistribute collagen/laminin- binding integrins. This study demonstrates that the human skin/severe combined immunodeficient chimera provides a useful model to study events during human wound repair.

Original languageEnglish
Pages (from-to)1458-1469
Number of pages12
JournalAmerican Journal of Pathology
Volume143
Issue number5
Publication statusPublished - Dec 1 1993

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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