Wounding-induced synthesis of hyaluronic acid in organotypic epidermal cultures requires the release of heparin-binding EGF and activation of the EGFR

47Citations
Citations of this article
44Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Hyaluronic acid (HA), a glycosaminoglycan located between keratinocytes in the epidermis, accumulates dramatically following skin wounding. To study inductive mechanisms, a rat keratinocyte organotypic culture model that faithfully mimics HA metabolism was used. Organotypic cultures were needle-punctured 100 times, incubated for up to 24 hours, and HA analyzed by histochemical and biochemical methods. Within 15 minutes post-injury, HA levels had elevated two-fold, increasing to four-fold by 24 hours. HA elevations far from the site of injury suggested the possible involvement of a soluble HA-inductive factor. Media transfer experiments (from wounded cultures to unwounded cultures) confirmed the existence of a soluble factor. From earlier evidence, we hypothesized that an EGF-like growth factor might be responsible. This was confirmed as follows: (1) EGFR kinase inhibitor (AG1478) completely prevented wounding-induced HA accumulation. (2) Rapid tyrosine-phosphorylation of EGFR correlated well with the onset of increased HA synthesis. (3) A neutralizing antibody that recognizes heparin binding EGF-like growth factor (HB-EGF) blocked wounding-induced HA synthesis by 50%. (4) Western analyses showed that release of activated HB-EGF (but neither amphiregulin nor EGF) occured after wounding. In summary, rapid HA accumulation after epidermal wounding occurs through a mechanism requiring cleavage of HB-EGF and activation of EGFR signaling. © 2009 The Society for Investigative Dermatology.

Cite

CITATION STYLE

APA

Monslow, J., Sato, N., MacK, J. A., & Maytin, E. V. (2009). Wounding-induced synthesis of hyaluronic acid in organotypic epidermal cultures requires the release of heparin-binding EGF and activation of the EGFR. Journal of Investigative Dermatology, 129(8), 2046–2058. https://doi.org/10.1038/jid.2009.9

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free