The 1,25-Dihydroxyvitamin D3-Independent Actions of the Vitamin D Receptor in Skin

April 2010 in “ Journal of steroid biochemistry and molecular biology/The Journal of steroid biochemistry and molecular biology ”

Diane R. Dowd, Paul N. MacDonald

Vitamin D Receptor VDR hair follicle cycling UV-induced skin carcinogenesis VDR knockout mice keratinocytes UVB exposure cell cycle arrest DNA repair apoptosis UV-induced skin cancer skin cells cell death

TLDR The vitamin D receptor helps regulate skin and hair health independently of its usual vitamin D ligand.

The study demonstrated that the Vitamin D Receptor (VDR) played a crucial role in skin homeostasis, hair follicle cycling, and protection against UV-induced skin carcinogenesis, independent of its ligand, 1,25-dihydroxyvitamin D3. VDR knockout mice exhibited hair follicle cycling defects, skin abnormalities, and 100% tumor development with chronic UVB exposure, unlike wild-type controls. VDR was essential for UV-induced cell cycle arrest, DNA repair, and apoptosis, and could control gene expression in keratinocytes without its traditional ligand. These findings suggested potential therapeutic targets for treating skin disorders and hair loss conditions.

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Research cited in this study

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research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

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180 citations , January 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

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research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

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research Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice

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research Normalization of Mineral Ion Homeostasis by Dietary Means Prevents Hyperparathyroidism, Rickets, and Osteomalacia, But Not Alopecia in Vitamin D Receptor-Ablated Mice

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research Alopecia Universalis Associated with a Mutation in the Human hairless Gene

412 citations , January 1998 in “Science”

The study investigated a kindred with a rare, recessively inherited type of alopecia universalis to identify the genetic basis of this condition. Through homozygosity mapping, researchers established linkage in a 6-centimorgan interval on chromosome 8p12, with a significant logarithm of the odds score of 6.19. They identified a missense mutation in the human homolog of the murine hairless gene within this interval. The human hairless gene encodes a putative single zinc finger transcription factor protein, which is expressed in the brain and skin, suggesting its role in the development of alopecia universalis.

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research The 1,25-Dihydroxyvitamin D3-Independent Actions of the Vitamin D Receptor in Skin

18 citations , April 2010 in “Journal of steroid biochemistry and molecular biology/The Journal of steroid biochemistry and molecular biology”

The vitamin D receptor helps regulate skin and hair health independently of its usual vitamin D ligand.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

Hairless protein can block vitamin D activation in skin cells.