Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes

Jia, Qian‐Nan

doi:10.7150/ijms.45765

Cited by 11 publications

(8 citation statements)

References 37 publications

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“…IL-13 activates the mTOR/mir-143 axis, which is followed by downregulation of IL-13a1, leading to an enhancement loop of IL-13 function and downregulation of epidermal barrier-related proteins. Preclinical studies of IL-13-stimulated HaCaT cells have shown that rapamycin can mediate this pathway and ease the effects of IL-13 in atopic dermatitis [55].…”

Section: Mtor Signaling In Atopic Dermatitismentioning

confidence: 99%

“…All key studies addressing the therapeutic approaches targeting mTOR signaling in skin diseases are summarized in Table 2. − reduction in their respective toxicities, notably cyclosporineinduced nephrotoxicities − antiproliferative and immunosuppressive characteristics [86] Everolimus combined with tacrolimus Case Report (renal transplant patient with psoriasis) − synergistic effect of everolimus and tacrolimus − resolution of the recalcitrant psoriatic manifestations − can ease the effects of IL-13 in atopic dermatitis [55] Pemphigus vulgaris…”

Section: Role Of Mtor Inhibitors In Melanomamentioning

confidence: 99%

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Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Karagianni

Pavlidis

Malakou

et al. 2022

IJMS

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The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncontrolled proliferation and inflammation, including skin hyperproliferative as well as malignant diseases. Herein, we provide an update on the current knowledge regarding the pathogenic implication of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice.

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Section: Mtor Signaling In Atopic Dermatitismentioning

confidence: 99%

Section: Role Of Mtor Inhibitors In Melanomamentioning

confidence: 99%

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Karagianni

Pavlidis

Malakou

et al. 2022

IJMS

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“…Of interest, it has been recently reported that Th2-released IL-13 could activate the mTOR signaling pathway in human immortalized keratinocytes, and the pharmacological inhibition of mTORC1 by rapamycin blocks the IL-13-induced expression of p-mTOR, p-S6K1, and p-AKT. Concomitantly, in human keratinocytes rapamycin upregulates the expression of terminal differentiation markers, including filaggrin, loricrin, and involucrin, typically impaired in AD skin lesions (89).…”

Section: Dual Effects Of Pi3k Pathways In Inflammatory and Hyperproliferative Skin Diseasesmentioning

confidence: 99%

Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

2021

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PhosphoInositide-3 Kinase (PI3K) represents a family of different classes of kinases which control multiple biological processes in mammalian cells, such as cell growth, proliferation, and survival. Class IA PI3Ks, the main regulators of proliferative signals, consists of a catalytic subunit (α, β, δ) that binds p85 regulatory subunit and mediates activation of AKT and mammalian Target Of Rapamycin (mTOR) pathways and regulation of downstream effectors. Dysregulation of PI3K/AKT/mTOR pathway in skin contributes to several pathological conditions characterized by uncontrolled proliferation, including skin cancers, psoriasis, and atopic dermatitis (AD). Among cutaneous cancers, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) display PI3K/AKT/mTOR signaling hyperactivation, implicated in hyperproliferation, and tumorigenesis, as well as in resistance to apoptosis. Upregulation of mTOR signaling proteins has also been reported in psoriasis, in association with enhanced proliferation, defective keratinocyte differentiation, senescence-like growth arrest, and resistance to apoptosis, accounting for major parts of the overall disease phenotypes. On the contrary, PI3K/AKT/mTOR role in AD is less characterized, even though recent evidence demonstrates the relevant function for mTOR pathway in the regulation of epidermal barrier formation and stratification. In this review, we provide the most recent updates on the role and function of PI3K/AKT/mTOR molecular axis in the pathogenesis of different hyperproliferative skin disorders, and highlights on the current status of preclinical and clinical studies on PI3K-targeted therapies.

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“…Finally, miR-143 has been found downregulated in the lesional skin from AD patients [ 79 ]. It targets IL-13 receptor alpha 1 ( IL13R ), modulating IL-13 activity.…”

Section: Role Of Mirnas In the Skin Pathogenesis Of Cutaneous Immumentioning

confidence: 99%

MicroRNAs in Several Cutaneous Autoimmune Diseases: Psoriasis, Cutaneous Lupus Erythematosus and Atopic Dermatitis

Domingo

Solé

Moliné

et al. 2020

Cells

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MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate the gene expression at a post-transcriptional level and participate in maintaining the correct cell homeostasis and functioning. Different specific profiles have been identified in lesional skin from autoimmune cutaneous diseases, and their deregulation cause aberrant control of biological pathways, contributing to pathogenic conditions. Detailed knowledge of microRNA-affected pathways is of crucial importance for understating their role in skin autoimmune diseases. They may be promising therapeutic targets with novel clinical implications. They are not only present in skin tissue, but they have also been found in other biological fluids, such as serum, plasma and urine from patients, and therefore, they are potential biomarkers for the diagnosis, prognosis and response to treatment. In this review, we discuss the current understanding of the role of described miRNAs in several cutaneous autoimmune diseases: psoriasis (Ps, 33 miRNAs), cutaneous lupus erythematosus (CLE, 2 miRNAs) and atopic dermatitis (AD, 8 miRNAs). We highlight their role as crucial elements implicated in disease pathogenesis and their applicability as biomarkers and as a novel therapeutic approach in the management of skin inflammatory diseases.

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Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes

Cited by 11 publications

References 37 publications

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

MicroRNAs in Several Cutaneous Autoimmune Diseases: Psoriasis, Cutaneous Lupus Erythematosus and Atopic Dermatitis

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