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Publication : The effects of KH 1060, a potent 20-epi analogue of the vitamin D3 hormone, on hairless mouse skin in vivo.

First Author  Gniadecki R Year  1995
Journal  Br J Dermatol Volume  132
Issue  6 Pages  841-52
PubMed ID  7662562 Mgi Jnum  J:26905
Mgi Id  MGI:74331 Doi  10.1111/j.1365-2133.1995.tb16939.x
Citation  Gniadecki R, et al. (1995) The effects of KH 1060, a potent 20-epi analogue of the vitamin D3 hormone, on hairless mouse skin in vivo. Br J Dermatol 132(6):841-52
abstractText  Dermal effects of KH 1060, a novel, highly potent 20-epi analogue of 1 alpha,25-dihyroxyvitamin D3, were investigated in a hairless mouse model. During daily topical applications of a 0.4 microM 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) beta 1-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 1 alpha,25-dihydroxyvitamin D3 were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D3 and 1 beta,25-dihydroxyvitamin D3, 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 (1 beta,25-dihydroxyvitamin D3) of this pathway. Our findings provide the first evidence that a strong vitamin D3 analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of epidermis-derived TGF-beta 1.
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