Mechanistic target of rapamycin (mTOR) expression is increased in acne patients' skin

Monfrecola, Giuseppe; Lembo, Serena; Caiazzo, Giuseppina; Vita, Valerio De; Caprio, Roberta Di; Balato, Anna; Fabbrocini, Gabriella

doi:10.1111/exd.12885

Cited by 99 publications

(95 citation statements)

References 9 publications

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“…Therefore, reducing S6K1 activity via mTORC1 inhibition could increase mTORC2 activity through either of these pathways in response to UVB. Upregulation of both mTOR and S6K1 has also been observed in the lesioned skin of a variety of inflammatory skin conditions [71, 72]. It would be interesting to determine whether mTORC1 inhibition has a similar effect on mTORC2 activity in these conditions.…”

Section: Discussionmentioning

confidence: 99%

Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation

Feehan

Shantz

2016

Cellular Signalling

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Exposure to ultraviolet-B (UVB) irradiation, the principal cause of non-melanoma skin cancer (NMSC), activates both the rapamycin-sensitive mammalian target of rapamycin complex 1 (mTORC1) and the rapamycin-resistant mTORC2. We have previously reported that UVB-induced keratinocyte survival is dependent on mTORC2, though the specific mechanism is not well understood. FOXO3a is an important transcription factor involved in regulating cell survival. The activity of FOXO3a is reduced as a result of protein kinase B (AKT/PKB) activation, which is downstream of mTORC2; however, the specific function of FOXO3a during UVB-induced apoptosis is unclear. In this study, we establish that in cells with wild-type mTORC2 activity, FOXO3a is quickly phosphorylated in response to UVB and sequestered in the cytoplasm. In contrast, loss of mTORC2 causes FOXO3a to be localized to the nucleus and sensitizes cells to UVB-induced apoptosis. Furthermore, this sensitization is rescued by knockdown of FOXO3a. Taken together, these studies provide strong evidence that inhibition of mTORC2 enhances UVB-induced apoptosis in a FOXO3a-dependent manner, and suggest that FOXO3a activation by mTORC2 inhibitors may be a valuable chemopreventive target in NMSC.

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Section: Discussionmentioning

confidence: 99%

Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation

Feehan

Shantz

2016

Cellular Signalling

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“…[1] SomeinflammatoryskindiseasesarecharacterizedbyelevatedlevelsofmTOR, [4][5][6] andtherearefewreports indicating an increase of mTOR and S6K1 in psoriasis too. [4,7] Up tonow,thelinkbetweenmTORC1andTNF-α in psoriasis has not beenyetelucidatedeventhoughitiswellknownthatTNF-α is an upstream signal of mTORC1 and also one of main protagonists of the disease.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic target of rapamycin complex 1 is involved in psoriasis and regulated by anti‐TNF‐α treatment

Balato

Lembo

Ayala

et al. 2017

Experimental Dermatology

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The mechanistic target of rapamycin (mTOR) acts through two distinct signalling complexes,\ud known as mTOR complex (mTORC) 1 and mTORC2. One of the main upstream regulator of\ud mTORC1 is tumour necrosis factor (TNF)-α, an important pro-inflammatory cytokine involved in\ud psoriasis. When active, mTORC1 phosphorylates and activates its downstream effector ribosomal protein S6 kinase 1 (S6K1) which is also found increased in psoriasis. Thus, the aim of the study\ud was to assess the involvement of mTORC1 signalling as well as to shed a light on the possible\ud relationship between mTORC1 and TNF-α in psoriasis. Our results showed that mTOR, S6K1 and,\ud in particular, its active form P-S6K1 were increased in psoriatic plaque, suggesting a specific\ud involvement of mTORC1 pathway in the disease. Moreover, for the first time, we reported that PS6K1\ud was completely abolished after anti-TNF-α therapy, indicating a stronger action of anti-TNF-\ud α agent on mTORC1

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“…Exaggerated expression of mechanistic target of rapamycin (mTOR), fueled by the Western diet, is increased in patients with acne. However, this association, mediated by conserved serine/threonine kinase (mTORC1), has been found to be present even in the absence of metabolic disease or insulin resistance and emerges as a determinant factor in the appearance of acne [74]. Acne appears clinically as inflammatory lesions on the mandibular area, neck, chest, and upper back.…”

Section: Introductionmentioning

confidence: 99%

Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management

González-Saldivar

Rodríguez-Gutiérrez

Ocampo‐Candiani

et al. 2016

Dermatol Ther (Heidelb)

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Worldwide, more than 1.9 billion adults are overweight, and around 600 million people suffer from obesity. Similarly, ~382 million individuals live with diabetes, and 40–50% of the global population is labeled at “high risk” (i.e., prediabetes). The impact of these two chronic conditions relies not only on the burden of illnesses per se (i.e., associated increased morbidity and mortality), but also on their increased cost, burden of treatment, and decreased health-related quality of life. For this review a comprehensive search in several databases including PubMed (MEDLINE), Ovid EMBASE, Web of Science, and Scopus was conducted. In both diabetes and obesity, genetic, epigenetic, and environmental factors overlap and are inclusive rather than exclusive. De facto, 70–80% of the patients with obesity and virtually every patient with type 2 diabetes have insulin resistance. Insulin resistance is a well-known pathophysiologic factor in the development of type 2 diabetes, characteristically appearing years before its diagnosis. The gold standard for insulin resistance diagnosis (the euglycemic insulin clamp) is a complex, invasive, costly, and hence unfeasible test to implement in clinical practice. Likewise, laboratory measures and derived indexes [e.g., homeostasis model assessment of insulin resistance (HOMA-IR-)] are indirect, imprecise, and not highly accurate and reproducible tests. However, skin manifestations of insulin resistance (e.g., acrochordons, acanthosis nigricans, androgenetic alopecia, acne, hirsutism) offer a reliable, straightforward, and real-time way to detect insulin resistance. The objective of this review is to aid clinicians in recognizing skin manifestations of insulin resistance. Diagnosing these skin manifestations accurately may cascade positively in the patient’s health by triggering an adequate metabolic evaluation, a timely treatment or referral with the ultimate objective of decreasing diabetes and obesity burden, and improving the health and the quality of care for these patients.

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Mechanistic target of rapamycin (mTOR) expression is increased in acne patients' skin

Cited by 99 publications

References 9 publications

Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation

Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation

Mechanistic target of rapamycin complex 1 is involved in psoriasis and regulated by anti‐TNF‐α treatment

Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management

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