The Vitamin D Receptor Is Required for Activation of CWnt and Hedgehog Signaling in Keratinocytes

September 2014 in “ Molecular Endocrinology ”

Lisse, Thomas S., Saini Vaibhav, Zhao Heng-guang, Luderer, Hilary F., Gori Francesca, Demay Marie B.

vitamin D receptor VDR cWnt signaling hedgehog signaling keratinocytes alopecia anagen chromatin immunoprecipitation Lef1 hair loss hair cycle skin cells

Studysummary This study found that the absence of unliganded vitamin D receptor significantly impairs cWnt and hedgehog signaling pathways necessary for hair cycle initiation in VDR-null mice.

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Research cited in this study

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research Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair

52 citations , April 2013 in “Developmental Cell”

This study found that Brg1, a chromatin-remodeling enzyme, plays a critical role in hair regeneration and early epidermal repair by regulating bulge stem cells through a Brg1-Shh interaction.

research Lymphoid Enhancer-Binding Factor-1 Interacts with the DNA-Binding Domain of the Vitamin D Receptor

37 citations , April 2011 in “Journal of Biological Chemistry”

This study discovered a novel interaction between the vitamin D receptor and LEF1, essential for normal Wnt signaling in keratinocytes, which is crucial for regular hair cycling.

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

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

This study found that mice lacking the Vitamin D receptor showed disrupted hair follicle cycling, which was partially restored with hedgehog signaling pathway activation, suggesting a role for this pathway in follicle regulation independent of vitamin D.

research Epidermal Homeostasis: A Balancing Act of Stem Cells in the Skin

1039 citations , February 2009 in “Nature Reviews Molecular Cell Biology”

This review discusses the reuse of molecular mechanisms involved in embryonic skin development for maintaining adult epidermal homeostasis and reports no new results.

research The Vitamin D Receptor Is a Wnt Effector That Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis

127 citations , January 2008 in “PloS one”

This study observed that the vitamin D receptor is crucial for hair follicle formation and altering tumor development in the Wnt signaling pathway, suggesting therapeutic potential for vitamin D analogues in related tumors.

research Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

143 citations , May 2007 in “Proceedings of the National Academy of Sciences”

This study found that absence of the vitamin D receptor in keratinocytes impairs canonical Wnt signaling and leads to alopecia due to defects in keratinocyte stem cells.

research Modulation of Hair Growth with Small Molecule Agonists of the Hedgehog Signaling Pathway

113 citations , September 2005 in “Journal of Investigative Dermatology”

This study found that a topical hedgehog agonist can stimulate hair growth by promoting the transition from the resting to growth phase of the hair cycle in adult mouse skin.

research Expression Profiling and Cellular Localization of Genes Associated with the Hair Cycle Induced by Wax Depilation

27 citations , August 2005 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study identified 12 new genes associated with the hair follicle and various stages of the hair cycle in mice, which could lead to novel targets for hair growth or depilation therapies.

research Defining the Impact of Beta-Catenin/Tcf Transactivation on Epithelial Stem Cells

384 citations , June 2005 in “Genes & development”

This study found that stabilized beta-catenin is crucial for activating stem cell transition from quiescence to proliferation in hair follicles by influencing gene expression within the stem cell niche.

research Cyclic Alopecia in Msx2 Mutants: Defects in Hair Cycling and Hair Shaft Differentiation

158 citations , December 2002 in “Development”

In this study, Msx2-deficient mice showed progressive hair loss due to shortened anagen phase and prolonged catagen and telogen phases, resulting in cyclic alopecia with structurally abnormal hair shafts.

research Expression of ΔNLef1 in Mouse Epidermis Results in Differentiation of Hair Follicles into Squamous Epidermal Cysts and Formation of Skin Tumors

297 citations , January 2002 in “Development”

In this study, repressing β-catenin/Lef1 signalling in mouse epidermis led to progressive hair loss, dermal cysts, and spontaneous skin tumors with sebaceous differentiation, indicating altered keratinocyte differentiation and potential tumourigenic processes.

research Lack of the Vitamin D Receptor Is Associated with Reduced Epidermal Differentiation and Hair Follicle Growth

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

This study observed that vitamin D receptor knockout mice exhibit impaired epidermal differentiation and progressive hair loss, suggesting the importance of the vitamin D receptor in normal skin and hair follicle development.

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

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

research Metabolic And Cellular Analysis Of Alopecia In Vitamin D Receptor Knockout Mice

137 citations , April 2001 in “Journal of Clinical Investigation”

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

114 citations , June 2000 in “Endocrinology”

In this study, the researchers found that alopecia in VDR null mice is likely due to issues with hair cycle initiation rather than defects in keratinocyte proliferation or differentiation.

research Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

990 citations , October 1999 in “Development”

This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.

research Induction of the Hair Growth Phase in Postnatal Mice by Localized Transient Expression of Sonic Hedgehog

231 citations , October 1999 in “Journal of Clinical Investigation”

This study found that administering an adenovirus vector to increase Sonic hedgehog gene expression in mouse skin accelerated the transition of hair follicles into the growth phase, promoting hair growth.

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

519 citations , October 1998 in “Endocrinology”

The study found that normalizing mineral ion levels in vitamin D receptor-ablated mice prevented hyperparathyroidism and bone disorders but did not address hair loss, indicating the VDR's role in hair growth.