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

November 2013 in “ Journal of Endocrinology/Journal of endocrinology ”

Jui Cheng Hsieh, Rudolf C. Estess, Ichiro Kaneko, G. Kerr Whitfield, Peter W. Jurutka, Mark R. Haussler

vitamin D receptor VDR 1,25-dihydroxyvitamin D3 1,25D DKKL1 Soggy SOSTDC1 Wise HR Hairless keratinocytes vitamin D responsive elements VDREs thyroid hormone receptor BMP signaling Wnt signaling hair cycle epidermal function

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.

View this study on joe.bioscientifica.com →

Discuss this study in the Community →

Cited in this study

16 / 16 results

research Hairless Modulates Ligand-Dependent Activation of the Vitamin D Receptor-Retinoid X Receptor Heterodimer

28 citations , January 2012 in “Biological & pharmaceutical bulletin”

Hairless protein can both repress and activate vitamin D receptor functions, affecting gene regulation.

research Vitamin D and the Skin: Physiology and Pathophysiology

158 citations , August 2011 in “Reviews in endocrine and metabolic disorders”

Vitamin D and its receptor regulate skin functions like cell growth, immunity, hair cycle, and tumor prevention.

research Disruption of the Hedgehog Signaling Pathway Contributes to Hair Follicle Cycling Deficiency in VDR Knockout Mice

53 citations , August 2010 in “Journal of Cellular Physiology”

Mice without Vitamin D receptors have hair growth problems because of issues in the hedgehog signaling pathway.

research Marie Unna Hereditary Hypotrichosis Caused by a Novel Mutation in the Human Hairless Transcript

14 citations , July 2010 in “Experimental Dermatology”

A new mutation in the HR gene causes hair loss in a specific family.

research Loss-Of-Function Mutations of an Inhibitory Upstream ORF in the Human Hairless Transcript Cause Marie Unna Hereditary Hypotrichosis

181 citations , January 2009 in “Nature Genetics”

Certain mutations in a hair growth-related gene cause a type of genetic hair loss.

research Alopecia: Association with Resistance to Thyroid Hormones

8 citations , January 2009 in “Journal of pediatric endocrinology & metabolism/Journal of pediatric endocrinology and metabolism”

A specific thyroid hormone resistance mutation may be linked to different types of hair loss.

research Thyroid Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte Proliferation and Hair Pigmentation

115 citations , November 2008 in “The Journal of Clinical Endocrinology & Metabolism”

Thyroid hormones help hair grow, reduce hair loss, and increase hair pigment.

research Ligand-Independent Regulation of the Hairless Promoter by Vitamin D Receptor

10 citations , February 2008 in “Photochemistry and photobiology”

Vitamin D receptor can control the hairless gene linked to hair loss even without vitamin D.

research Interactions of the Vitamin D Receptor with the Corepressor Hairless

42 citations , August 2007 in “Journal of Biological Chemistry”

Most Hairless gene mutations reduce its ability to work with the Vitamin D Receptor, which might explain a certain type of hair loss.

research Evidence for 1,25-Dihydroxyvitamin D3-Independent Transactivation by the Vitamin D Receptor

36 citations , April 2007 in “Journal of biological chemistry/The Journal of biological chemistry”

The vitamin D receptor can work without its usual activating molecule.

research Hairless and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

74 citations , September 2006 in “Cell Cycle”

The HR protein's role as a repressor is essential for controlling hair growth.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , January 2006 in “Endocrinology”

Hairless protein can block vitamin D activation in skin cells.

research Hairless Triggers Reactivation of Hair Growth by Promoting Wnt Signaling

137 citations , September 2005 in “Proceedings of the National Academy of Sciences of the United States of America”

The HR protein helps hair grow by blocking a hair growth inhibitor, aiding in hair follicle regeneration.

research Atrichia Caused by Mutations in the Vitamin D Receptor Gene Is a Phenocopy of Generalized Atrichia Caused by Mutations in the Hairless Gene

139 citations , September 2001 in “The journal of investigative dermatology/Journal of investigative dermatology”

Mutations in the Vitamin D receptor gene can cause hair loss similar to mutations in the Hairless gene.

research Thyroid Hormone Receptor β1 Is Expressed in the Human Hair Follicle

111 citations , April 2000 in “British journal of dermatology/British journal of dermatology, Supplement”

Thyroid hormone receptor β1 is found in human hair follicles and helps them survive.

research The Hairless Gene of the Mouse: Relationship of Phenotypic Effects with Expression Profile and Genotype

52 citations , October 1999 in “Developmental Dynamics”

Mutations in the hairless gene in mice affect its expression and lead to a range of developmental issues in multiple tissues.