Cargando…

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment

This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne 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). A Weste...

Descripción completa

Detalles Bibliográficos
Autor principal: Melnik, Bodo C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670572/
https://www.ncbi.nlm.nih.gov/pubmed/37998335
http://dx.doi.org/10.3390/cells12222600
_version_ 1785139954447286272
author Melnik, Bodo C.
author_facet Melnik, Bodo C.
author_sort Melnik, Bodo C.
collection PubMed
description This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne 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). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The 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 the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The 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 the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin’s desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.
format Online
Article
Text
id pubmed-10670572
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106705722023-11-10 Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment Melnik, Bodo C. Cells Review This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne 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). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The 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 the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The 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 the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin’s desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin. MDPI 2023-11-10 /pmc/articles/PMC10670572/ /pubmed/37998335 http://dx.doi.org/10.3390/cells12222600 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Melnik, Bodo C.
Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title_full Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title_fullStr Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title_full_unstemmed Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title_short Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
title_sort acne transcriptomics: fundamentals of acne pathogenesis and isotretinoin treatment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670572/
https://www.ncbi.nlm.nih.gov/pubmed/37998335
http://dx.doi.org/10.3390/cells12222600
work_keys_str_mv AT melnikbodoc acnetranscriptomicsfundamentalsofacnepathogenesisandisotretinointreatment