mTORC1 and mTORC2 Levels in Patients With Psoriasis
Keywords:
psoriasis, mTORCsAbstract
Introduction: In recent years, the role of the mammalian target of rapamycin (mTOR) pathway, which is one of the intracellular signaling pathways and known as the main control pathway of metabolism, in the pathogenesis of psoriasis has been emphasized.
Objectives: We sought to investigate the importance of the mTOR pathway in the pathogenesis of psoriasis.
Methods: Forty patients with psoriasis and 40 healthy volunteers were included in this case-control study. Serum fasting mTORC1 and mTORC2 levels of the study groups were examined by enzyme-linked immunosorbent assay.
Results: Serum mTORC1 and mTORC2 levels were significantly lower in patients with psoriasis than controls (p= 0.001). A positive correlation was found between serum mTORC1 and serum mTORC2 levels in patients with psoriasis (p=0,001, r=0,826).
Conclusion: The lower serum levels of mTORC1 and mTORC2 complexes which are active signalling molecules in the cell, were found to be lower in patient with psoriasis, suggesting that it may be an indicator of increased intracellular activation of these molecules. Our opinion that agents that can effectively inhibit both mTOR complexes may be more effective in the treatment of psoriasis.
References
Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA. 2020;323(19):1945-60. doi: 10.1001/jama.2020.4006.
Yamanaka K, Yamamoto O, Honda T. Pathophysiology of psoriasis: A review. J Dermatol. 2021;48(6):722-31. doi: 10.1111/1346-8138.15913.
Szwed A, Kim E, Jacinto E. Regulation and metabolic functions of mTORC1 and mTORC2. Physiol Rev. 2021;101(3):1371-426. doi: 10.1152/physrev.00026.2020.
Ersahin T, Tuncbag N, Cetin-Atalay R. The PI3K/AKT/mTOR interactive pathway. Mol Biosyst. 2015;11(7):1946-54. doi: 10.1039/c5mb00101c.
Liu Y, Zhang DT, Liu XG. mTOR signaling in T cell immunity and autoimmunity. Int Rev Immunol. 2015;34(1):50-66. doi: 10.3109/08830185.2014.933957.
Wang J, Cui B, Chen Z, Ding X. The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling. Front Cell Dev Biol. 2022;10:950973. doi: 10.3389/fcell.2022.950973.
Ding X, Bloch W, Iden S, Ruegg MA, Hall MN, Leptin M, et al. mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation. Nat Commun. 2016;7:13226. doi: 10.1038/ncomms13226.
Karagianni F, Pavlidis A, Malakou LS, Piperi C, Papadavid E. Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential. Int J Mol Sci. 2022;23(3). doi: 10.3390/ijms23031693.
Buerger C, Malisiewicz B, Eiser A, Hardt K, Boehncke WH. Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin. Br J Dermatol. 2013;169(1):156-9. doi: 10.1111/bjd.12271.
Buerger C, Shirsath N, Lang V, Berard A, Diehl S, Kaufmann R, et al. Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation. PLoS One. 2017;12(7):e0180853. doi: 10.1371/journal.pone.0180853.
Ochaion A, Bar-Yehuda S, Cohen S, Barer F, Patoka R, Amital H, et al. The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease. Cell Immunol. 2009;258(2):115-22. doi: 10.1016/j.cellimm.2009.03.020.
Cao W, Manicassamy S, Tang H, Kasturi SP, Pirani A, Murthy N, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat Immunol. 2008;9(10):1157-64. doi: 10.1038/ni.1645.
Fan X, Shen Z, Wang G, YuFeng L. Is CCR7 a potential target for biologic therapy in psoriasis? Increased expression of CCR7 in psoriasis vulgaris. Indian J Dermatol Venereol Leprol. 2008;74(5):550. doi: 10.4103/0378-6323.44338.
Kuwabara T, Tanaka Y, Ishikawa F, Kondo M, Sekiya H, Kakiuchi T. CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-kappa B pathway in dendritic cells. J Leukoc Biol. 2012;92(2):309-18. doi: 10.1189/jlb.0811415.
Perl A. Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases. Nat Rev Rheumatol. 2016;12(3):169-82. doi: 10.1038/nrrheum.2015.172.
Mitra A, Raychaudhuri SK, Raychaudhuri SP. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine. 2012;60(1):38-42. doi: 10.1016/j.cyto.2012.06.316.
Huang T, Lin X, Meng X, Lin M. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target? Acta Derm Venereol. 2014;94(4):371-9. doi: 10.2340/00015555-1737.
Yu J, Zhao Q, Wang X, Zhou H, Hu J, Gu L, et al. Pathogenesis, multi-omics research, and clinical treatment of psoriasis. J Autoimmun. 2022;133:102916. doi: 10.1016/j.jaut.2022.102916.
Cheng Mm W, Long Y, Wang H, Han Mm W, Zhang J, Cui N. Role of the mTOR Signalling Pathway in Human Sepsis-Induced Myocardial Dysfunction. Can J Cardiol. 2019;35(7):875-83. doi: 10.1016/j.cjca.2019.03.022.
Schreiber KH, Ortiz D, Academia EC, Anies AC, Liao CY, Kennedy BK. Rapamycin-mediated mTORC2 inhibition is determined by the relative expression of FK506-binding proteins. Aging Cell. 2015;14(2):265-73. doi: 10.1111/acel.12313.
Raychaudhuri SK, Raychaudhuri SP. mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target. Indian J Dermatol. 2014;59(1):67-70. doi: 10.4103/0019-5154.123499.
Chamcheu JC, Adhami VM, Esnault S, Sechi M, Siddiqui IA, Satyshur KA, et al. Dual Inhibition of PI3K/Akt and mTOR by the Dietary Antioxidant, Delphinidin, Ameliorates Psoriatic Features In Vitro and in an Imiquimod-Induced Psoriasis-Like Disease in Mice. Antioxid Redox Signal. 2017;26(2):49-69. doi: 10.1089/ars.2016.6769.
Roy T, Banang-Mbeumi S, Boateng ST, Ruiz EM, Chamcheu RN, Kang L, et al. Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation. Front Immunol. 2022;13:1075804. doi: 10.3389/fimmu.2022.1075804.
Liu Z, Fan Y, Zhang Z, Fang Y, Cheng X, Yang Q, et al. mTOR in the Mechanisms of Atherosclerosis and Cardiovascular Disease. Discov Med. 2021;31(164):129-40.
Sarandi E, Krueger-Krasagakis S, Tsoukalas D, Sidiropoulou P, Evangelou G, Sifaki M, et al. Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy. Front Mol Biosci. 2023;10:1201912. doi: 10.3389/fmolb.2023.1201912.
Loyola K, Karsulovic C, Cabrera R, Perez C, Hojman L. New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity. Metabolites. 2023;13(1). doi: 10.3390/metabo13010116.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 İlayda Esna Gülsunay, İlknur Altunay, Tuğba Kum, Asli Aksu Cerman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Dermatology Practical & Conceptual applies a Creative Commons Attribution License (CCAL) to all works we publish (http://creativecommons.org/licenses/by-nc/4.0/). Authors retain the copyright for their published work.
How to Cite
Share
