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Acneigenic Stimuli Converge in Phosphoinositol-3 Kinase/ Akt/Foxo1 Signal Transduction

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Author(s): Dr. Bodo C. Melnik

Journal: Journal of Clinical & Experimental Dermatology Research
ISSN 2155-9554

Volume: 1;
Issue: 1;
Date: 2010;
Original page

Keywords: Acne | Acne variants | Acneigenic stimuli | Phosphoinositol-3 kinase/Akt | FoxO1

ABSTRACT
The complex multifactorial pathogenesis of acne vulgaris, the most common skin disease, may be explained at the level of genomic regulation. A recent hypothesis suggested that a relative nuclear defi ciency of the metabolic sensor and nuclear transcription factor FoxO1 appears to play a key role in the pathogenesis of acne vulgaris. FoxO1 has been identifi ed as an important regulator of androgen receptor, cell proliferation, apoptosis, lipogenesis, oxidative stress regulation, innate and acquired immunity, all important aspects involved in the pathogenesis of acne. It is the intention of this review article to provide further evidence for the potential function of the PI3K/Akt/FoxO1 signaling pathway for other types of acne and acne-like eruptions. Apparently unrelated acneigenic stimuli like hyperglycemic food, insulinotropic milk and dairy product consumption, smoking, psychological stress, fibroblast growth factor receptor-2 mutations in Apert syndrome and acneiform nevus, chloracne, and antidepressant-induced acne are all associated with upregulated PI3K/Akt-signaling known to result in a nuclear deficiency of FoxO1. Reduced nuclear levels of FoxO1 may increase the expression of important acne target genes and derepress nuclear receptors, suggested to be involved in the clinical manifestation of acne. Accumulating indirect evidence supports the role of growth factor- and growth factorlike acneigenic stimuli in posttranslational modifi cation of nuclear FoxO1 and strenghtens the hypothesis of a nuclear FoxO1 deficiency as the possible underlying cause of acne vulgaris and clinical acne variants. This review intends to stimulate future research activities on the promising PI3K/Akt/FoxO1 signaling pathway which may be most helpful to unravel the pathogenesis of acne.
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