Review
Version 1
Preserved in Portico This version is not peer-reviewed
Acne Transcriptomics: Fundamentals in Acne Pathogenesis and Isotretinoin Treatment
Version 1
: Received: 8 October 2023 / Approved: 9 October 2023 / Online: 9 October 2023 (07:48:02 CEST)
A peer-reviewed article of this Preprint also exists.
Melnik, B.C. Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment. Cells 2023, 12, 2600. Melnik, B.C. Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment. Cells 2023, 12, 2600.
Abstract
This review provides information on acne transcriptomics allowing deeper insights into acne pathogenesis and isotretinoin´s mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). Western diet (hyperglycemic carbohydrates, milk/dairy products) as well co-stimulate AKT/mTORC1 signaling. AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch, which enhances the transactivation of lipogenic and proinflammatory transcription factors including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ), and signal transducer and activator of transcription 3 (STAT3) but reduces FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor of infundibular keratinocyte homeostasis. AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in sebaceous glands of acne patients. Overexpression of these proapoptotic transcription factors explains isotretinoin´s desired sebum-suppressive effect via induction of sebocyte apoptosis but also its adverse effects including teratogenicity (neural crest cell apoptosis), reduced ovarian reserve (granulosa cell apoptosis), risk of depression (apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.
Keywords
acne; apoptosis; FoxO1; FoxO3; isotretinoin; mTORC1; p53; pathogenesis; therapy; transcriptomics
Subject
Medicine and Pharmacology, Dermatology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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