Vitamin D Receptor-Mediated Control of Soggy, Wise, and Hairless Gene Expression in Keratinocytes

    Jui Cheng Hsieh, Rudolf C. Estess, Ichiro Kaneko, G. Kerr Whitfield, Peter W. Jurutka, Mark R. Haussler
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    TLDR Vitamin D receptor helps control hair growth genes in skin cells.
    The study demonstrated that the vitamin D receptor (VDR), independent of its ligand 1,25-dihydroxyvitamin D3 (1,25D), played a crucial role in regulating the expression of genes involved in the hair cycle. Specifically, DKKL1 (Soggy) and SOSTDC1 (Wise) mRNA levels were repressed by 41-72% in keratinocytes upon 1,25D treatment, with functional vitamin D responsive elements (VDREs) identified in their respective genes. Conversely, HR (Hairless) mRNA was upregulated 1.56- to 2.77-fold by 1,25D, with a VDRE identified that mediated this induction even without the ligand. Additionally, a thyroid hormone responsive element was found in the HR gene, suggesting a complex regulatory mechanism involving both VDR and thyroid hormone receptor. The proposed model indicated that unliganded VDR upregulated HR expression, which then repressed DKKL1 and SOSTDC1, integrating BMP and Wnt signaling to drive the hair cycle and influence epidermal function.
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