Transforming growth factor-β1 modulates β1 and β5 integrin receptors and induces the de novo expression of the avβ6 heterodimer in normal human keratinocytes: Implications for wound healing

Giovanna Zambruno, Pier Carlo Marchisio, Alessandra Marconi, Cristina Vaschieri, Antonella Melchiori, Alberto Giannetti, Michele De Luca

Research output: Contribution to journalArticle

Abstract

The molecular mechanism underlying the promotion of wound healing by TGF-β1 is incompletely understood. We report that TGF-β1 regulates the regenerative/migratory phenotype of normal human keratinocytes by modulating their integrin receptor repertoire. In growing keratinocyte colonies but not in fully stratified cultured epidermis, TGF-β1: (a) strongly upregulates the expression of the fibronectin receptor α5β1 the vitronectin receptor α5β1, and the collagen receptor α2β1 by differentially modulating the synthesis of their α and β subunits; (b) downregulates the multifunctional α3β1 heterodimer; (c) induces the de novo expression and surface exposure of the αvβ6 fibronectin receptor; (d) stimulates keratinocyte migration toward fibronectin and vitronectin; (e) induces a marked perturbation of the general mechanism of polarized domain sorting of both β1 and β4 dimers; and (f) causes a pericellular redistribution of αvβ5. These data suggest that α5β1, αvβ6 and αvβ5 not routinely used by keratinocytes resting on an intact basement membrane, act as "emergency" receptors, and uncover at least one of the molecular mechanisms responsible for the peculiar integrin expression in healing human wounds. Indeed, TGF-β1 reproduces the integrin expression pattern of keratinocytes located at the injury site, particularly of cells in the migrating epithelial tongue at the leading edge of the wound. Since these keratinocytes are inhibited in their proliferative capacity, these data might account for the apparent paradox of a TGF-β1-dependent stimulation of epidermal wound healing associated with a growth inhibitory effect on epithelial cells.

Original languageEnglish
Pages (from-to)853-865
Number of pages13
JournalJournal of Cell Biology
Volume129
Issue number3
Publication statusPublished - May 1995

ASJC Scopus subject areas

  • Cell Biology

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