The hyaluronan synthesis inhibitor 4-methylumbelliferone prevents keratinocyte activation and epidermal hyperproliferation induced by epidermal growth factor

The Journal of Investigative Dermatology
Kirsi RillaRaija H Tammi

Abstract

Since excessive epidermal hyaluronan is associated with hyperproliferative states and disturbed terminal differentiation of the keratinocytes, we hypothesized that 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan synthesis, could counteract these phenotypic features. Cultured epidermal keratinocytes showed a concentration dependent, maximum 83% reduction of hyaluronan in the presence of 0.2-1.0 mM 4-MU, whereas less decline was seen in the synthesis of chondroitin and heparan sulfate. The reduced hyaluronan was associated with no apparent change in its molecular mass. The 4-MU-treated keratinocytes showed an accentuated epithelial morphology with a flat, round cell shape, increased stress fibers and large vinculin-positive adhesion plaques, cytoskeletal changes consistent with the markedly reduced migration rate observed in scratched monolayer cultures. High concentrations of 4-MU also caused a block in keratinocyte proliferation, reversible upon 4-MU withdrawal. In the epidermis of organotypic cultures, 4-MU prevented the hyaluronan accumulation and epidermal hypertrophy induced by epidermal growth factor. The present results concur with earlier data indicating that enhanced cell locomotion and proliferation are associ...Continue Reading

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Citations

Sep 10, 2009·The Journal of Biological Chemistry·Davide VigettiAlberto Passi
Mar 31, 2007·American Journal of Respiratory Cell and Molecular Biology·Dahis ManzanaresMatthias Salathe
Jun 25, 2008·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Kirsi RillaRaija Tammi
Jul 29, 2008·Connective Tissue Research·Tiina A JokelaMarkku I Tammi
Jan 19, 2008·The Journal of Physiology·K R IngramJ R Levick
Apr 28, 2005·The Journal of Investigative Dermatology·Raija TammiMarkku Tammi
Jul 16, 2009·The Journal of Investigative Dermatology·Raija H Tammi, Markku I Tammi
Mar 25, 2014·The Journal of Investigative Dermatology·Jérémy MalaisseYves Poumay
Oct 4, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zsuzsanna Pályi-KrekkPeter Nagy
Mar 8, 2013·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Tiina A JokelaMarkku I Tammi
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Jul 15, 2005·The Journal of Biological Chemistry·Kirsi RillaRaija H Tammi
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Dec 29, 2020·Journal of Dermatological Science·Yoko EndoYoshito Takahashi
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Oct 1, 2020·Biochemical and Biophysical Research Communications·Kosuke KasaiToshiya Nakamura
Mar 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Marisa AssunçãoAnna Blocki
Jun 4, 2021·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Robert B VernonThomas N Wight
Oct 18, 2005·Matrix Biology : Journal of the International Society for Matrix Biology·T S MombergerR M Mason

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