Survivin as a Novel Biomarker in the Pathogenesis of Acne Vulgaris and Its Correlation to Insulin-Like Growth Factor-I

Assaf, Hanan; Abdel-Maged, Wafaa M.; Elsadek, Bakheet; Hassan, Mohammed H.; Adly, Mohamed A.; Ali, Soher A.

doi:10.1155/2016/7040312

Cited by 29 publications

(36 citation statements)

References 54 publications

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“…Our study confirms the hypothesis that isotretinoin treatment of acne patients increases nuclear levels of FoxO1 and FoxO3 proteins . FoxOs operate as nuclear transcription factors that are critically involved in apoptotic signalling and apparently contribute to sebocyte apoptosis, the key mechanism explaining isotretinoin′s sebum‐suppressive effect . Isotretinoin ( 13‐cis‐ retinoic acid) exerts its specific activity on human sebocytes through selective intracellular isomerization to all‐trans retinoic acid (ATRA) and binding to retinoic acid receptors (RARs) .…”

Section: Discussionsupporting

confidence: 82%

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Agamia

Roshdy

Abdelmaksoud

et al. 2018

Experimental Dermatology

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Oral isotretinoin is the most effective anti‐acne drug with the strongest sebum‐suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin‐induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro‐apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non‐phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne‐free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo‐cytoplasmic ratio of non‐phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin‐induced pro‐apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin‐mediated upregulation of FoxO expression.

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Section: Discussionsupporting

confidence: 82%

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Agamia

Roshdy

Abdelmaksoud

et al. 2018

Experimental Dermatology

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“…In fact, an increased risk of PCa has been observed in men who suffered from more severe Av, which required oral tetracycline treatment [ 106 ]. Notably, increased IGF-1 and AR-mediated signaling with increased expression of survivin are related to both Av and PCa [ 88 , 106 – 109 ]. Among patients diagnosed with localized PCa, compared to men who consumed <1 servings/day of high-fat milk, those who drank ≥3 servings/day had an increased hazard of PCa mortality [ 110 ].…”

Section: Introductionmentioning

confidence: 99%

“…Serum levels of IGF-1, a key stimulator of mTORC1 activity [ 118 – 125 ], increase during milk intake [ 124 , 125 ]. Enhanced IGF-1 signaling has been related with the pathology of both Av [ 109 , 126 – 129 ] and PCa [ 130 ], respectively. A recent meta-analysis substantiated a significant association between milk consumption and increased IGF-1 serum levels in patients with PCa [ 130 ].…”

Section: Introductionmentioning

confidence: 99%

Milk disrupts p53 and DNMT1, the guardians of the genome: implications for acne vulgaris and prostate cancer

Melnik

2017

Nutr Metab (Lond)

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There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks. TP53 regulates the expression of key genes involved in cell homeostasis such as FOXO1, PTEN, SESN1, SESN2, AR, IGF1R, BAK1, BIRC5, and TNFSF10. Nuclear interaction of p53 with DNMT1 controls gene silencing. The most abundant miRNA of milk and milk fat, miRNA-148a, directly targets DNMT1. Reduced DNMT1 expression further attenuates the activity of histone deacetylase 1 (HDAC1) involved in the regulation of chromatin structure and access to transcription. The presented milk-mediated miRNA-p53-DNMT1 pathway exemplified at the promoter regulation of survivin (BIRC5) provides a novel explanation for the epidemiological association between milk consumption and acne vulgaris and prostate cancer. Notably, p53- and DNMT1-targeting miRNAs of bovine and human milk survive pasteurization and share identical seed sequences, which theoretically allows the interaction of bovine miRNAs with the human genome. Persistent intake of milk-derived miRNAs that attenuate p53- and DNMT1 signaling of the human milk consumer may thus present an overlooked risk factor promoting acne vulgaris, prostate cancer, and other p53/DNMT1-related Western diseases. Therefore, bioactive miRNAs of commercial milk should be eliminated from the human food chain.

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“…Similarly, WWB/DD complex significantly prevented IGF-I production induced by LPS. During puberty, IGF-I signaling may have a causal role in the pathogenesis of acne by influencing adrenal and gonadal androgen metabolism that was reported to be an inducer of sebum production through sterol response element-binding proteins [24,25]. Recently, the involvement of IGF-I, but not androgens, has been suggested in acne pathogenesis [26].…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic Effects of White Willow Bark and 1,2-Decanediol on Human Adult Keratinocytes

Bassino

Gasparri

Munaron

2017

Skin Pharmacol Physiol

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Background: Acne vulgaris is a common skin defect, usually occurring during adolescence, but often it can persist in adults leaving permanent face scarring. Acne is usually treated with topical drugs, oral antibiotics, retinoids, and hormonal therapies, but medicinal plants are increasingly employed. Objective: To investigate the protective role of white willow bark (WWB) and 1,2-decanediol (DD) on the damage caused by lipopolysaccharides (LPS) on human adult keratinocytes (HaCaT). Methods: HaCaT were exposed to LPS alone or in association with WWB and DD. Epidermal viability, metabolic modulation, inflammatory activity, and cell migration were assessed with both common standardized protocols or high-throughput screening systems. Results: The preincubation of HaCaT with WWB and DD (used separately or in combination) differently prevented the alterations induced by LPS on HaCaT in terms of growth factor release (IGF, EGF, VEGF), cytokine production (IL-1α, IL-6, IL-8), or expression of the transcription factor FOXO-I. Moreover, they partially restore wound repair lowered by LPS. Conclusions: These results suggest that both natural compounds were able to differently affect several functions of LPS-stressed keratinocytes suggesting their potential role for the prevention of acne vulgaris, without adverse effects.

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Survivin as a Novel Biomarker in the Pathogenesis of Acne Vulgaris and Its Correlation to Insulin-Like Growth Factor-I

Cited by 29 publications

References 54 publications

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris

Milk disrupts p53 and DNMT1, the guardians of the genome: implications for acne vulgaris and prostate cancer

Pleiotropic Effects of White Willow Bark and 1,2-Decanediol on Human Adult Keratinocytes

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