Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy

Autor: Mads A. Røpke, Georg Dünstl, Hanne Norsgaard, Tatiana Gonzalez, Troels Marstrand, Sandrine Kurdykowski, Pascal Descargues
Rok vydání: 2014
Předmět:
Zdroj: Archives of Dermatological Research
ISSN: 1432-069X
0340-3696
DOI: 10.1007/s00403-014-1485-3
Popis: The calcipotriol/betamethasone dipropionate fixed-combination gel is widely used for topical treatment of psoriasis vulgaris. It has been hypothesized that calcipotriol counteracts glucocorticoid-induced skin atrophy which is associated with changes in the extracellular matrix (ECM). To elucidate the combined effects of calcipotriol and betamethasone on key ECM components, a comparative study to the respective mono-treatments was carried out. The effect on collagen I synthesis, matrix metalloproteinase (MMP) secretion, and hyaluronic acid (HA) production was investigated in primary human fibroblast and keratinocyte cultures as well as in a human skin explant model. We show that calcipotriol counteracts betamethasone-induced suppression of collagen I synthesis. Similarly, calcipotriol and betamethasone have opposing effects on MMP expression in both fibroblasts and keratinocytes. Moreover, calcipotriol is able to restore betamethasone-impaired HA synthesis in keratinocytes and prevent betamethasone-induced epidermal thinning in minipigs upon treatment with the calcipotriol/betamethasone gel. In summary, our results show for the first time in primary human skin cultures that calcipotriol reduces early signs of betamethasone-induced skin atrophy by modulation of key ECM components. These results indicate that the calcipotriol component of the fixed-combination gel counteracts the atrophogenic effects of betamethasone on the skin. Electronic supplementary material The online version of this article (doi:10.1007/s00403-014-1485-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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