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Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis
Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa‐microRNA‐31‐5p (miR‐31) i...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086589/ https://www.ncbi.nlm.nih.gov/pubmed/36855912 http://dx.doi.org/10.15252/emmm.202215674 |
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author | Wang, Mao‐Jie Huang, Huan‐Jie Xu, Yong‐Yue Vos, Harmjan Gulersonmez, Can Stigter, Edwin Gerritsen, Johan Gallego, Marc Pages van Es, Robert Li, Li Deng, Hao Han, Lin Huang, Run‐Yue Lu, Chuan‐Jian Burgering, Boudewijn MT |
author_facet | Wang, Mao‐Jie Huang, Huan‐Jie Xu, Yong‐Yue Vos, Harmjan Gulersonmez, Can Stigter, Edwin Gerritsen, Johan Gallego, Marc Pages van Es, Robert Li, Li Deng, Hao Han, Lin Huang, Run‐Yue Lu, Chuan‐Jian Burgering, Boudewijn MT |
author_sort | Wang, Mao‐Jie |
collection | PubMed |
description | Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa‐microRNA‐31‐5p (miR‐31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR‐31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR‐31‐induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31‐induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis. |
format | Online Article Text |
id | pubmed-10086589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100865892023-04-12 Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis Wang, Mao‐Jie Huang, Huan‐Jie Xu, Yong‐Yue Vos, Harmjan Gulersonmez, Can Stigter, Edwin Gerritsen, Johan Gallego, Marc Pages van Es, Robert Li, Li Deng, Hao Han, Lin Huang, Run‐Yue Lu, Chuan‐Jian Burgering, Boudewijn MT EMBO Mol Med Articles Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa‐microRNA‐31‐5p (miR‐31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR‐31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR‐31‐induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31‐induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis. John Wiley and Sons Inc. 2023-03-01 /pmc/articles/PMC10086589/ /pubmed/36855912 http://dx.doi.org/10.15252/emmm.202215674 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Wang, Mao‐Jie Huang, Huan‐Jie Xu, Yong‐Yue Vos, Harmjan Gulersonmez, Can Stigter, Edwin Gerritsen, Johan Gallego, Marc Pages van Es, Robert Li, Li Deng, Hao Han, Lin Huang, Run‐Yue Lu, Chuan‐Jian Burgering, Boudewijn MT Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title | Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title_full | Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title_fullStr | Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title_full_unstemmed | Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title_short | Metabolic rewiring in keratinocytes by miR‐31‐5p identifies therapeutic intervention for psoriasis |
title_sort | metabolic rewiring in keratinocytes by mir‐31‐5p identifies therapeutic intervention for psoriasis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086589/ https://www.ncbi.nlm.nih.gov/pubmed/36855912 http://dx.doi.org/10.15252/emmm.202215674 |
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