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Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response
Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351483/ https://www.ncbi.nlm.nih.gov/pubmed/32695877 http://dx.doi.org/10.1126/sciadv.aaz8272 |
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author | Akbar, Moeed Garcia-Melchor, Emma Chilaka, Sabarinadh Little, Kevin J. Sood, Shatakshi Reilly, James H. Liew, Foo Y. McInnes, Iain B. Millar, Neal L. |
author_facet | Akbar, Moeed Garcia-Melchor, Emma Chilaka, Sabarinadh Little, Kevin J. Sood, Shatakshi Reilly, James H. Liew, Foo Y. McInnes, Iain B. Millar, Neal L. |
author_sort | Akbar, Moeed |
collection | PubMed |
description | Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren’s disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren’s as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease. |
format | Online Article Text |
id | pubmed-7351483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73514832020-07-20 Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response Akbar, Moeed Garcia-Melchor, Emma Chilaka, Sabarinadh Little, Kevin J. Sood, Shatakshi Reilly, James H. Liew, Foo Y. McInnes, Iain B. Millar, Neal L. Sci Adv Research Articles Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren’s disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren’s as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease. American Association for the Advancement of Science 2020-07-10 /pmc/articles/PMC7351483/ /pubmed/32695877 http://dx.doi.org/10.1126/sciadv.aaz8272 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Akbar, Moeed Garcia-Melchor, Emma Chilaka, Sabarinadh Little, Kevin J. Sood, Shatakshi Reilly, James H. Liew, Foo Y. McInnes, Iain B. Millar, Neal L. Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title | Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title_full | Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title_fullStr | Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title_full_unstemmed | Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title_short | Attenuation of Dupuytren’s fibrosis via targeting of the STAT1 modulated IL-13Rα1 response |
title_sort | attenuation of dupuytren’s fibrosis via targeting of the stat1 modulated il-13rα1 response |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351483/ https://www.ncbi.nlm.nih.gov/pubmed/32695877 http://dx.doi.org/10.1126/sciadv.aaz8272 |
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