Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Karagianni, Fani; Pavlidis, Antreas; Malakou, Lina S.; Piperi, Christina; Papadavid, Evangelia

doi:10.3390/ijms23031693

Cited by 40 publications

(36 citation statements)

References 99 publications

(148 reference statements)

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“…It was obvious that the diosmin nanocrystals were more effective than diosmin powder gel in suppressing the expression of the aforementioned proteins expression in the skin of psoriatic rats. It has been reported that intracellular signaling pathway AKT/m-TOR/P70S6K was activated in the skin of psoriatic patients and in skin of mice treated with Imiquimod leading to uncontrolled epidermal cells proliferation (13,14). Additionally, our results revealed signi cant elevation in the expression of PCNA in the skin of untreated psoriatic rats, indicating an increased level of cell proliferation.…”

Section: Discussionsupporting

confidence: 58%

“…Also it has been found that AKT signaling molecule is activated in skin of psoriatic patients and in skin of mice treated with IMQ. The activated AKT can subsequently activate mammalian target of rapamycin (mTOR) and its downstream signalling molecule p70 ribosomal protein S6 kinase (P70S6K) that can nally have a great role in elevated condition of uncontrolled epidermal cells proliferation (13,14). This is con rmed by the elevated expression of PCNA that is a marker of psoriatic epidermal proliferation (15).…”

Section: Introductionmentioning

confidence: 99%

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Diosmin nanocrystals alleviate Imiquimod induced psoriasis in rats via modulating TLR7,8/ NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu and Tregs / Th17 balance

Shahine

El-Aal²,

Reda³

et al. 2022

Preprint

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Diosmin is a flavonoidal compound characterized by highly challenging physicochemical properties. There wasn’t enough attention paid for using diosmin topically in spite of its strong anti-inflammatory and anti-oxidant properties. The aim of this work is the development and characterization of diosmin nanocrystals using anti-solvent precipitation technique to be used for topical treatment of psoriasis. Evaluation of different stabilizers with different concentrations to achieve the most stable nanocrystals was studied. Results revealed that diosmin nanocrystals stabilized with hydroxypropyl methylcellulose (HPMC E15) in weight ratio (diosmin:polymer 1:1) could reach the desired particle size (276.9 ± 16.49 nm); provided the promising colloidal properties and higher drug release profile. In-vivo assessment was carried out to evaluate and compare the activities of diosmin nanocrystals gel using 3 different doses and diosmin powder gel in alleviating imiquimod induced psoriasis in rats and investigating their possible anti-inflammatory mechanisms. Herein, 125 mg of 5% imiquimod cream (IMQ) was applied topically for 5 consecutive days on the shaved backs of rats to induce psoriasis. Diosmin nanocrystals gel especially in the highest dose used offered the best anti-inflammatory effect. This was confirmed by causing the most significant mitigation in the psoriasis area severity index (PASI) score and the serum inflammatory cytokines levels (IL17A, IL23, and IL22). Furthermore, it was capable of maintaining balance between Th17 and Treg cells by decreasing the immunohistochemical expression of RORγ and increasing that of FOXP3. Moreover, it tackled TLR7/8/NF-κB, AKT/mTOR/P70S6K and elevated the TNFAIP3/A20 (negative regulator of NF-κB) expression in psoriatic skin tissues. Also, it abrogated the tissue expression of PCNA, BCL-2 and miRNA-31 level. This highlights the role of diosmin nanocrystals gel in tackling imiquimod induced psoriasis in rats via modulating TLR7,8/NF-κB/miRNA-31, AKT/mTOR/P70S6K milieu and Tregs/Th17 balance. Therefore, it is suggested that diosmin nanocrystals gel could be a novel promising therapy for psoriasis.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Diosmin nanocrystals alleviate Imiquimod induced psoriasis in rats via modulating TLR7,8/ NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu and Tregs / Th17 balance

Shahine

El-Aal²,

Reda³

et al. 2022

Preprint

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“…Remarkably, patients with topical application of mTORC1 inhibitor showed relieved rosacea symptoms (Deng et al, 2021). Taken together, these findings strongly demonstrate the altered epidermal mTOR signaling status under skin inflammatory disease conditions and suggest that inhibition of mTOR signaling activity as a promising treatment for inflammatory skin disease in general (Karagianni et al, 2022).…”

Section: Mechanistic Target Of Rapamycin and Inflammatory Skin Diseasesmentioning

confidence: 64%

The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling

Wang

Cui

Chen

et al. 2022

Front. Cell Dev. Biol.

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The epidermis, the outmost layer of the skin, is a stratified squamous epithelium that protects the body from the external world. The epidermis and its appendages need constantly renew themselves and replace the damaged tissues caused by environmental assaults. The mechanistic target of rapamycin (mTOR) signaling is a central controller of cell growth and metabolism that plays a critical role in development, homeostasis and diseases. Recent findings suggest that mTOR signaling is activated in a spatiotemporal and context-dependent manner in the epidermis, coordinating diverse skin homeostatic processes. Dysregulation of mTOR signaling underlies the pathogenesis of skin diseases, including psoriasis and skin cancer. In this review, we discuss the role of epidermal mTOR signaling activity and function in skin, with a focus on skin barrier formation, hair regeneration, wound repair, as well as skin pathological disorders. We propose that fine-tuned control of mTOR signaling is essential for epidermal structural and functional integrity.

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“…A possible influence of the gut microbiota in acne may be an interaction with the mTOR (mammalian target of rapamycin) pathway. Recent studies have shown an impaired mTOR pathway in various skin diseases [ 92 ]. In general, mTOR is a nutrient-sensitive regulator that participates in processes of cell growth and differentiation in the skin, being key in homeostasis and in forming an appropriate epidermal barrier [ 93 ].…”

Section: Acne Vulgaris and Gut Microbiotamentioning

confidence: 99%

Acne, Microbiome, and Probiotics: The Gut–Skin Axis

et al. 2022

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The objective of this narrative review was to check the influence of the human microbiota in the pathogenesis of acne and how the treatment with probiotics as adjuvant or alternative therapy affects the evolution of acne vulgaris. Acne is a chronic inflammatory skin disease involving the pilosebaceous units. The pathogenesis of acne is complex and multifactorial involving genetic, metabolic, and hormonal factors in which both skin and gut microbiota are implicated. Numerous studies have shown the bidirectionality between the intestinal microbiota and skin homeostasis, a communication mainly established by modifying the immune system. Increased data on the mechanisms of action regarding the relevance of Cutibacterium acnes, as well as the importance of the gut–skin axis, are becoming known. Diverse and varied in vitro studies have shown the potential beneficial effects of probiotics in this context. Clinical trials with both topical and oral probiotics are scarce, although they have shown positive results, especially with oral probiotics through the modulation of the intestinal microbiota, generating an anti-inflammatory response and restoring intestinal integrity, or through metabolic pathways involving insulin-like growth factor I (IGF-1). Given the aggressiveness of some standard acne treatments, probiotics should continue to be investigated as an alternative or adjuvant therapy.

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Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Cited by 40 publications

References 99 publications

Diosmin nanocrystals alleviate Imiquimod induced psoriasis in rats via modulating TLR7,8/ NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu and Tregs / Th17 balance

Diosmin nanocrystals alleviate Imiquimod induced psoriasis in rats via modulating TLR7,8/ NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu and Tregs / Th17 balance

The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling

Acne, Microbiome, and Probiotics: The Gut–Skin Axis

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