ArticleThe Journal of allergy and clinical immunology2017
A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis.
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- Selected traditional Chinese herbal medicines for the treatment of atopic dermatitis - research progress on the effect and mechanism of actions.Frontiers in pharmacology · 2025Review
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- Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.Cell death & disease · 2024Article
- Immunomodulatory potential of primary cilia in the skin.Frontiers in immunology · 2024Review
- Review
- Obesity-induced immunological effects on the skin.Skin health and disease · 2023Review
- Anti-inflammatory effects of amarogentin on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like mice and in HaCat cells.Animal models and experimental medicine · 2023Article
- mTORC1 Deficiency Prevents the Development of MC903-Induced Atopic Dermatitis through the Downregulation of Type 2 Inflammation.International journal of molecular sciences · 2023Article
- Article
- Article
- Review
- Revisiting the Roles of Filaggrin in Atopic Dermatitis.International journal of molecular sciences · 2022Review
- Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential.International journal of molecular sciences · 2022Review
- Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.Frontiers in cell and developmental biology · 2022Review
- The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling.Frontiers in cell and developmental biology · 2022Review
- Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation.Cell death and differentiation · 2021Article
- A positive feedback loop between mTORC1 and cathelicidin promotes skin inflammation in rosacea.EMBO molecular medicine · 2021Article
- Therapeutic effects of quinine in a mouse model of atopic dermatitis.Molecular medicine reports · 2021Article
- Improvement of Atopic Dermatitis by Synbiotic Baths.Microorganisms · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundFilaggrin, which is encoded by the filaggrin gene (FLG), is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations.
objectiveWe hypothesized that these patients might possess other defects in filaggrin expression and processing contributing to barrier disruption and AD, and therefore we present novel therapeutic targets for this disease.
resultsWe describe the relationship between the mechanistic target of rapamycin complex 1/2 protein subunit regulatory associated protein of the MTOR complex 1 (RAPTOR), the serine/threonine kinase V-Akt murine thymoma viral oncogene homolog 1 (AKT1), and the protease cathepsin H (CTSH), for which we establish a role in filaggrin expression and processing. Increased RAPTOR levels correlated with decreased filaggrin expression in patients with AD. In keratinocyte cell cultures RAPTOR upregulation or AKT1 short hairpin RNA knockdown reduced expression of the protease CTSH. Skin of CTSH-deficient mice and CTSH short hairpin RNA knockdown keratinocytes showed reduced filaggrin processing, and the mouse had both impaired skin barrier function and a mild proinflammatory phenotype.
conclusionOur findings highlight a novel and potentially treatable signaling axis controlling filaggrin expression and processing that is defective in patients with AD.
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