Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth

Okano, Jun-ichi; Levy, Clara; Lichti, Ulrike; Sun, Hongwei; Yuspa, Stuart H.; Sakai, Yasuo; Morasso, María I.

doi:10.1074/jbc.m112.397273

Cited by 31 publications

(32 citation statements)

References 55 publications

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“…Furthermore knock-out mouse lacking Cyp26b1 in their skin exhibit major hair follicle development defects [27]. By acting on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, RA modulates pathways and factors implicated in hair follicle downgrowth and bending [27]. In the human and mouse cicatricial alopecia and alopecia areata, retinoid metabolism is altered and genes involved in RA synthesis increases, while RA degradation genes are decreased [81,82].…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

“…In the human and mouse cicatricial alopecia and alopecia areata, retinoid metabolism is altered and genes involved in RA synthesis increases, while RA degradation genes are decreased [81,82]. Appropriate RA metabolism is needed for the normal formation of the hair follicle [6,27,81,82].…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

“…In a mouse model which knocked out cytochrome P450, family 26, subfamily b, polypeptide 1 (Cyp26b1), which encodes an RA-degrading enzyme, the in vivo administration of RA to pregnant mice or its addition to skin cultures demonstrated that appropriate RA levels are important for periderm desquamation, embryonic skin differentiation, and barrier formation in the developing mammalian skin [26]. Furthermore knock-out mouse lacking Cyp26b1 in their skin exhibit major hair follicle development defects [27]. By acting on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, RA modulates pathways and factors implicated in hair follicle downgrowth and bending [27].…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

“…A frequent adverse effect of these therapies is RA-induced hair loss [62,80]. The mechanisms to explain how excess RA arrests hair follicle growth have been explored [27,62]. ATRA induces a catagen-like stage in human hair follicles, presumably via up-regulation of TGF-β2 in the dermal papilla, resulting in hair loss [62].…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

“…Interestingly, ATRA-induced expression of Tgm2 (transglutaminase 2) and Gbx1 in the epidermis and that of TGF-β2 expression in the dermis are required for the mucosal transdifferentiation [22]. Other than the transdifferentiation, RA also plays an important role in barrier formation and hair follicle formation in skin [6,7,[23][24][25][26][27]. This review highlights our current understanding of the role of retinoic acid in the epidermal transdifferentiation of skin and its appendages.…”

Section: Introductionmentioning

confidence: 99%

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Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Akimoto

Miyaji

Morimoto-Kamata

et al. 2014

JDB

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Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470-488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal OPEN ACCESS J. Dev. Biol. 2014, 2 159 epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

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Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Akimoto

Miyaji

Morimoto-Kamata

et al. 2014

JDB

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The Skin and Endocrine Disorders

Paus

2016

Rook's Textbook of Dermatology, Ninth Edition

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Given that the skin is a major target organ of numerous hormones for which it expresses functional receptors, it is not surprising that excessive or insufficient systemic levels of these hormones induce clinically relevant cutaneous responses. These can manifest as general skin symptoms and signs such as pruritus, skin dryness, seborrhoea, hair loss, hypertrichosis, hirsutism, hyperhidrosis and/or hyperpigmentation, any of which prompts consideration of an underlying endocrine disease. In addition, characteristic skin lesions such as palmar erythema, gingival hyperpigmentation, stretch marks (striae distensae), acanthosis nigricans, pretibial myxoedema, necrobiosis lipoidica, melasma and acneform eruptions provide invaluable diagnostic clues to the possibility of unrecognized endocrine disease. More recently, the field has been revolutionized by the recognition that human skin is also a major endocrine and neuroendocrine organ which produces and/or metabolizes not only all classes of steroid hormones but also multiple peptide (neuro‐) hormones, neuropeptides and neurotransmitters. These impact profoundly on skin physiology and pathology at multiple levels, ranging from skin barrier function and neurogenic skin inflammation via wound healing to cutaneous stress responses. This has important implications for future dermatological therapy.

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The Skin and Endocrine Disorders

Paus,

Ramot

2024

Rook's Textbook of Dermatology

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Endocrine disorders can exert major effects on the human skin, leading to different signs and symptoms, including skin dryness, hair loss or excessive hair growth, pruritus, pigmentary changes and hyperhidrosis. This chapter reviews these changes and provides a practical approach to patients with suspected underlying endocrinological disorders. The chapter also discusses the latest findings showing that the skin serves as a complex (neuro‐) endocrine organ by itself, and thus possesses important practical implications for future dermatological therapy.

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Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth

Cited by 31 publications

References 55 publications

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

The Skin and Endocrine Disorders

The Skin and Endocrine Disorders

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