The Role of the Vitamin D Receptor in the Epidermal Stem Cell Response to Wounding

August 2024 in “ Receptors ”

Daniel D. Bikle

vitamin D receptor VDR epidermal stem cells wound healing hair follicle interfollicular epidermis 1,25(OH)2D SRC 2 SRC 3 mediator complex calcium metabolism stem cells skin

Studysummary This review highlights the crucial role of vitamin D signaling in epidermal stem cells during skin wound healing, emphasizing its distinct functions from calcium metabolism and its importance in genomic regulation mediated by the vitamin D receptor.

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The review discusses the critical role of the Vitamin D Receptor (VDR) in the epidermal stem cell (SC) response to skin wounding. VDR, through its ligand 1,25(OH)2D, regulates genomic changes in SCs, enabling them to contribute to wound healing by altering their cell fate. The VDR's actions are modulated by coregulators like SRC 2, SRC 3, and the mediator complex (MED), and it often works in conjunction with other transcription factors such as p63 and β-catenin. Mice lacking VDR show impaired wound healing due to reduced SC activation and migration, and failure to form E-cadherin/catenin complexes necessary for re-epithelialization. The findings underscore the importance of VDR in maintaining skin integrity and facilitating effective wound healing, distinct from its traditional role in calcium metabolism. Further research is needed to fully understand its mechanisms.

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research Vitamin D Receptor Cross-Talk With P63 Signaling Promotes Epidermal Cell Fate

1 citations , June 2023 in “Journal of steroid biochemistry and molecular biology/The Journal of steroid biochemistry and molecular biology”

This study found that deleting the vitamin D receptor from specific stem cells in mouse hair follicles disrupts their ability to regenerate the epidermis after injury, suggesting an essential interaction with the transcription factor p63.

research Wound-Induced Hair Neogenesis: A Portal to the Development of New Therapies for Hair Loss and Wound Regeneration

16 citations , September 2022 in “Cold Spring Harbor Perspectives in Biology”

This article explores how adult mammals can regenerate hair follicles after wounding and suggests that manipulating cell signals during healing might enhance this process, but provides no new experimental results.

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378 citations , February 2020 in “Nature Reviews Endocrinology”

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211 citations , November 2018 in “Nature Cell Biology”

This article discusses the coordinated roles of different epidermal stem cells and other cell types in the skin's wound healing process and reports no new experimental results.

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209 citations , October 2018 in “Cell Reports”

This study found that Lgr5 and Lgr6 stem cells both activated wound-healing genes, but only Lgr5 stem cells changed their identity to contribute to new skin formation during wound repair.

Vitamin D Receptor Is Required for Proliferation, Migration, and Differentiation of Epidermal Stem Cells and Progeny During Cutaneous Wound Repair

research Vitamin D Receptor Is Required for Proliferation, Migration, and Differentiation of Epidermal Stem Cells and Progeny During Cutaneous Wound Repair

46 citations , May 2018 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that the vitamin D receptor is essential for the self-renewal, migration, and differentiation of epidermal stem cells during skin wound healing in mice.

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28 citations , March 2017 in “Endocrinology”

In this study, the researchers found that vitamin D and calcium signaling in keratinocytes are essential for normal skin regeneration after wounding, with deficiencies significantly delaying wound closure and re-epithelialization in mice.

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132 citations , January 2017 in “International Journal of Molecular Sciences”

This review explores how adipose-derived stem cells contribute to skin homeostasis and highlights recent advances in their clinical applications in dermatology, but it reports no new clinical results.

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86 citations , August 2015 in “The Journal of Steroid Biochemistry and Molecular Biology”

This study suggests that vitamin D and calcium signaling play a crucial role in wound healing by regulating stem cell activation through enhanced β-catenin transcriptional activity in mice.

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

56 citations , September 2014 in “Molecular Endocrinology”

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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426 citations , August 2014 in “Nature Medicine”

This narrative review examines the interactions between skin stem cells and their niches, finding new insights from advancements in genetic and imaging tools but reporting no new experimental results.

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96 citations , July 2014 in “Cold Spring Harbor Perspectives in Medicine”

This review discusses various stem cell compartments in adult murine and human epidermis, examining their expressed markers and characterization assays, and reports no new experimental results.

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238 citations , March 2013 in “Development”

This study found that adipocytes play a crucial role in skin wound healing by facilitating fibroblast recruitment and dermal reconstruction during the healing process.

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65 citations , November 2012 in “Tissue Engineering Part B-reviews”

This review discusses the biology of hair follicle stem cells and highlights their potential for applications in regenerative medicine, drug, and gene delivery, but reports no new clinical results.

research Ligand-Dependent Actions of the Vitamin D Receptor Are Required for Activation of TGF-Beta Signaling During the Inflammatory Response to Cutaneous Injury

56 citations , November 2012 in “Endocrinology”

This study found that the absence of vitamin D receptor signaling in mice impairs the inflammatory response to skin injury, particularly affecting macrophage recruitment and granulation tissue formation.

research Epithelial Stem Cells And Implications For Wound Repair

156 citations , October 2012 in “Seminars in Cell & Developmental Biology”

This study found that hair follicle stem cells initially contribute to wound re-epithelialization, but long-lasting epidermal cells are primarily derived from a stem cell population in the isthmus portion of hair follicles.

research Dissecting the Bulge in Hair Regeneration

86 citations , February 2012 in “Journal of Clinical Investigation”

This review discusses recent advances in understanding hair follicle stem cell dynamics and interactions, but it reports no new experimental findings.

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25 citations , March 2008 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study suggests that while VDR is crucial for maintaining hair follicles in mice, their degeneration may be linked to impaired cell migration during hair growth phases rather than stem cell loss.

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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.

Role of β-Catenin in Epidermal Stem Cell Expansion, Lineage Selection, and Cancer