Retinoids – Which Dermatological Indications Will Benefit in the Near Future?

Zouboulis, Christos C.

doi:10.1159/000056361

Cited by 119 publications

(102 citation statements)

References 67 publications

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“…These ligand-dependent transcription factors bind retinoids either as homodimers (RAR/RAR, RXR/RXR) or heterodimers (RAR/RXR) [4], which then can induce subsequent target gene expression by binding to the retinoid-responsive elements (RAREs and RXREs) in the promotor region of such genes [5, 6, 7]. They also inhibit the expression of genes without retinoid-responsive elements by downregulating the action of other transcription factors such as activator protein-1 (AP-1) and nuclear factor for interleukin-6 (NF-IL6), probably through mechanisms of competition for commonly required co-activator proteins [8, 9, 10].…”

Section: Topical Retinoidsmentioning

confidence: 99%

Topical Treatment in Acne: Current Status and Future Aspects

Gollnick

Krautheim²

2003

Dermatology

110

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During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2–5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO₂ laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.

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Section: Topical Retinoidsmentioning

confidence: 99%

Topical Treatment in Acne: Current Status and Future Aspects

Gollnick

Krautheim²

2003

Dermatology

110

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“…Several of the pathways regulated by TAF4 play important roles in epidermal homeostasis. The TGF␤ pathway restricts keratinocyte proliferation in the adult epidermis (Wang, 2001) and T-RA is an important regulator of keratinocyte function -T-RA and its derivatives being used to treat a variety of skin disorders (Futoryan and Gilchrest, 1994;Zouboulis, 2001).…”

Section: Introductionmentioning

confidence: 99%

The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis

et al. 2007

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The TAF4 subunit of transcription factor TFIID was inactivated in the basal keratinocytes of foetal and adult mouse epidermis. Loss of TAF4 in the foetal epidermis results in reduced expression of the genes required for skin barrier function, leading to early neonatal death. By contrast, TAF4 inactivation in adult epidermis leads to extensive fur loss and an aberrant hair cycle characterised by a defective anagen phase. Although the mutant epidermis contains few normal anagen-phase hair follicles, many genes expressed at this stage are strongly upregulated indicating desynchronised and inappropriate gene expression. The TAF4 mutant adult epidermis also displays interfollicular hyperplasia associated with a potent upregulation of several members of the EGF family of mitogens. Moreover, loss of TAF4 leads to malignant transformation of chemically induced papillomas and the appearance of invasive melanocytic tumours. Together, our results show that TAF4 is an important regulator of keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity.

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“…Dgat1 Ϫ/Ϫ mice exhibit a pleiotropic phenotype, which includes resistance to diet-induced obesity and altered energy metabolism but also includes prominent phenotypic findings in the skin (16 -19). Retinoids play key roles in skin and hair biology (20), and excess retinoids induce epidermal hyperplasia, inhibit sebocyte proliferation and differentiation, and alter hair growth (21). Notably, the skin manifestations of Dgat1 Ϫ/Ϫ mice, which include alopecia and sebaceous gland atrophy (18), resemble those of retinoid toxicity (22,23).…”

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confidence: 99%

Retinol Esterification by DGAT1 Is Essential for Retinoid Homeostasis in Murine Skin

Shih

Kane

Zhou

et al. 2009

Journal of Biological Chemistry

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Retinoic acid (RA) is a potent signaling molecule that is essential for many biological processes, and its levels are tightly regulated by mechanisms that are only partially understood. The synthesis of RA from its precursor retinol (vitamin A) is an important regulatory mechanism. Therefore, the esterification of retinol with fatty acyl moieties to generate retinyl esters, the main storage form of retinol, may also regulate RA levels. Here we show that the neutral lipid synthesis enzyme acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) functions as the major acyl-CoA:retinol acyltransferase (ARAT) in murine skin. When dietary retinol is abundant, DGAT1 deficiency results in elevated levels of RA in skin and cyclical hair loss; both are prevented by dietary retinol deprivation. Further, DGAT1-deficient skin exhibits enhanced sensitivity to topically administered retinol. Deletion of the enzyme specifically in the epidermis causes alopecia, indicating that the regulation of RA homeostasis by DGAT1 is autonomous in the epidermis. These findings show that DGAT1 functions as an ARAT in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity. Our findings may have implications for human skin or hair disorders treated with agents that modulate RA signaling.

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Retinoids – Which Dermatological Indications Will Benefit in the Near Future?

Cited by 119 publications

References 67 publications

Topical Treatment in Acne: Current Status and Future Aspects

Topical Treatment in Acne: Current Status and Future Aspects

The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis

Retinol Esterification by DGAT1 Is Essential for Retinoid Homeostasis in Murine Skin

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