Segmental hypopigmented acneiform nevus with FGFR2 gene mutation

Xie, Yongyi; Wu, Zhouwei

doi:10.1016/j.abd.2021.09.021

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…Patients with congenital fibroblast growth factor receptor 2 (FGFR2) gain-of-function mutations (S252W or P253R FGFR2)-either germline (Apert syndrome) [55][56][57][58] or segmental somatic (acne nevus of Munro) [59][60][61][62][63]-develop acne during puberty and respond to isotretinoin treatment [64]. FGFR2 is a tyrosine kinase receptor which, like INSR or IGF1R, activates multiple pathways, including PI3K/AKT signaling [55].…”

Section: Fgfr2-pi3k-akt-mediated Activation Of Mtorc1mentioning

confidence: 99%

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment

Melnik

2023

Cells

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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.

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Section: Fgfr2-pi3k-akt-mediated Activation Of Mtorc1mentioning

confidence: 99%

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment

Melnik

2023

Cells

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Acne Transcriptomics: Fundamentals in Acne Pathogenesis and Isotretinoin Treatment

Melnik

2023

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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.

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Segmental hypopigmented acneiform nevus with FGFR2 gene mutation

Cited by 2 publications

References 6 publications

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment

Acne Transcriptomics: Fundamentals in Acne Pathogenesis and Isotretinoin Treatment

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