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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
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.
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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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