Epidermal retinol dehydrogenases cyclically regulate stem cell markers and clock genes and influence hair composition

The hair follicle (HF) is a self-renewing adult miniorgan that undergoes drastic metabolic and morphological changes during precisely timed cyclic organogenesis. The HF cycle is known to be regulated by steroid hormones, growth factors and circadian clock genes. Recent data also suggest a role for a...

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Published in:Communications biology 2024-04, Vol.7 (1), p.453-12, Article 453
Main Authors: Goggans, Kelli R., Belyaeva, Olga V., Klyuyeva, Alla V., Studdard, Jacob, Slay, Aja, Newman, Regina B., VanBuren, Christine A., Everts, Helen B., Kedishvili, Natalia Y.
Format: Article
Language:English
Subjects:
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Adult
Biomedical and Life Sciences
Catalysis
Circadian rhythm
Circadian rhythms
Clock gene
Dehydrogenases
Epidermis
Gene expression
Growth factors
Hair
Humans
Life Sciences
Organogenesis
Retinoic acid
Retinoic acid receptors
Stem Cells
Steroid hormones
Transcription factors
Tretinoin
Vitamin A
Vitamin A - pharmacology
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Summary:The hair follicle (HF) is a self-renewing adult miniorgan that undergoes drastic metabolic and morphological changes during precisely timed cyclic organogenesis. The HF cycle is known to be regulated by steroid hormones, growth factors and circadian clock genes. Recent data also suggest a role for a vitamin A derivative, all- trans -retinoic acid (ATRA), the activating ligand of transcription factors, retinoic acid receptors, in the regulation of the HF cycle. Here we demonstrate that ATRA signaling cycles during HF regeneration and this pattern is disrupted by genetic deletion of epidermal retinol dehydrogenases 2 (RDHE2, SDR16C5) and RDHE2-similar (RDHE2S, SDR16C6) that catalyze the rate-limiting step in ATRA biosynthesis. Deletion of RDHEs results in accelerated anagen to catagen and telogen to anagen transitions, altered HF composition, reduced levels of HF stem cell markers, and dysregulated circadian clock gene expression, suggesting a broad role of RDHEs in coordinating multiple signaling pathways. Epidermal retinol dehydrogenases 2 (SDR16C5) and RDHE2-similar (SDR16C6) are the major retinol dehydrogenases in skin, which regulate hair cycling, hair composition, hair follicle stem cell markers, and circadian clock genes.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-06160-2