The effects of KH 1060, a potent 20‐epi analogue of the vitamin D3 hormone, on hairless mouse skin in vivo
2010
Dermal effects of KH 1060, a novel, highly potent 20-epi analogue of 1α,25-dihyroxyvitamin D 3 , were investigated in a hairless mouse model. During daily topical applications of a 0.4 μM solution of KH 1060 for 4 weeks, epidermal hyperplasia and an increase of dermal thickness and mass were observed. KH 1060 upregulated glycosaminoglycan and collagen synthesis in the skin, and increased glycosaminoglycan deposition in the subepidermal region. Reverse transcription-polymerase chain reaction amplification of the transforming growth factor (TGF) β1-specific mRNA revealed that KH 1060 stimulated expression of this growth factor in the epidermis, but not in the dermis. Changes observed after application of 1α,25-dihydroxyvitamin D 3 were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D 3 and 1β,25-dihydroxyvitamin D 3 , did not produce any effects. Furthermore, we were unable to demonstrate the involvement of the non-genomic, receptor-independent vitamin D signalling in the skin, using a specific stimulator (Ro 24-2090) and a blocker (1β,25-dihydroxyvitamin D 3 ) of this pathway. Our findings provide the first evidence that a strong vitamin D 3 analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of epidermis-derived TGF-β1.
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