Inhibition of putative hyalurosome platform in keratinocytes as a mechanism for corticosteroid-induced epidermal atrophy.

Abstract

The main limitation of using topical corticosteroids in dermatology is their atrophic effects on the skin. We have previously proposed a molecular platform composed of CD44, EGFR, and hyaluronate synthase (HAS) that is functionally defective in dermatoporosis, a chronic cutaneous insufficiency/fragility syndrome. In this study, we explored the molecular mechanisms of the skin atrophy induced by corticosteroids. We observed an important skin atrophy and a significant decrease of hyaluronic acid (HA), its main cell surface receptor CD44, and F-actin in mouse skin treated with topical clobetasol propionate (CP). Human keratinocytes exposed to CP showed an impaired HA secretion and diminished expression of CD44 and HAS3. CP also abolished filopodia of keratinocytes exposed to CP together with a redistribution of CD44 and F-actin depolymerization. We also show that HA fragments of intermediary size (HAFi) induced keratinocyte filopodia and protected them against CP. Topical HAFi induced hyperplasia in mouse epidermis and prevented CP-induced atrophy. Our results suggest that a CD44/EGFR/HAS platform associated with F-actin and filopodia of keratinocytes is the target of corticosteroids for their atrophogenic effects. These observations may lead to the development of new treatment and prevention strategies for corticosteroid-induced skin atrophy.

• Authors: Laurent Barnes, Frédérique Ino, Fabienne Jaunin, Jean-Hilaire Saurat, Gürkan Kaya
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 133 Issue 4 Pg. 1017-26 (Apr 2013) ISSN: 1523-1747 [Electronic] United States
• PMID: 23223147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cd44 protein, mouse
• Dermatologic Agents
• Glucocorticoids
• Hyaluronan Receptors
• Peptide Fragments
• Viscosupplements
• Hymecromone
• Hyaluronic Acid
• Clobetasol
• Glucuronosyltransferase
• Has3 protein, mouse
• Hyaluronan Synthases

Topics

• Animals
• Atrophy (chemically induced, metabolism, pathology)
• Cell Line, Transformed
• Clobetasol (pharmacology)
• Dermatologic Agents (pharmacology)
• Drug Interactions
• Epidermis (drug effects, metabolism, pathology)
• Glucocorticoids (pharmacology)
• Glucuronosyltransferase (metabolism)
• Homeostasis (drug effects)
• Hyaluronan Receptors (metabolism)
• Hyaluronan Synthases
• Hyaluronic Acid (chemistry, pharmacology)
• Hymecromone (analogs & derivatives, pharmacology)
• Keratinocytes (drug effects, metabolism, pathology)
• Mice
• Mice, Hairless
• Molecular Weight
• Peptide Fragments (chemistry, pharmacology)
• Pseudopodia (drug effects, metabolism, pathology)
• Skin Cream (pharmacology)
• Viscosupplements (chemistry, pharmacology)