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PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner
This study was aimed to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium (DSS)−, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and CD4+CD45Rb(hi) T cell transfer colitis model were established and analy...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228332/ https://www.ncbi.nlm.nih.gov/pubmed/25387791 http://dx.doi.org/10.1038/srep07023 |
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author | Wei, Fanhua Zhang, Yuying Jian, Jinlong Mundra, Jyoti Joshi Tian, Qingyun Lin, Jiqiang Lafaille, Juan Jose Tang, Wei Zhao, Weiming Yu, Xiuping Liu, Chuan-Ju |
author_facet | Wei, Fanhua Zhang, Yuying Jian, Jinlong Mundra, Jyoti Joshi Tian, Qingyun Lin, Jiqiang Lafaille, Juan Jose Tang, Wei Zhao, Weiming Yu, Xiuping Liu, Chuan-Ju |
author_sort | Wei, Fanhua |
collection | PubMed |
description | This study was aimed to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium (DSS)−, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and CD4+CD45Rb(hi) T cell transfer colitis model were established and analyzed in wild-type and several genetically-modified mice, including PGRN, IL-10 and TNFR2 deficient mice. Elevated levels of PGRN were found in colitis samples from human IBD patients and mouse colitis models in comparison to the corresponding controls. PGRN-deficient mice became highly susceptible to DSS- and TNBS-induced colitis, whereas recombinant PGRN ameliorated the pathology and reduced the histological score in both DSS and TNBS colitis models. In addition, hematopoietic-derived PGRN was critical for protection against DSS-induced colitis, and lack of PGRN signaling in CD4+ T cells also exacerbated experimental colitis. PGRN-mediated protective effect in colitis was compromised in the absence of IL-10 signaling. In addition, PGRN's effect was also largely lost in the TNFR2-deficient colitis model. Collectively, these findings not only provide the new insight into PGRN's anti-inflammatory action in vivo, but may also present PGRN and its derivatives as novel biological agent for treating IBD. |
format | Online Article Text |
id | pubmed-4228332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42283322014-11-13 PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner Wei, Fanhua Zhang, Yuying Jian, Jinlong Mundra, Jyoti Joshi Tian, Qingyun Lin, Jiqiang Lafaille, Juan Jose Tang, Wei Zhao, Weiming Yu, Xiuping Liu, Chuan-Ju Sci Rep Article This study was aimed to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium (DSS)−, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and CD4+CD45Rb(hi) T cell transfer colitis model were established and analyzed in wild-type and several genetically-modified mice, including PGRN, IL-10 and TNFR2 deficient mice. Elevated levels of PGRN were found in colitis samples from human IBD patients and mouse colitis models in comparison to the corresponding controls. PGRN-deficient mice became highly susceptible to DSS- and TNBS-induced colitis, whereas recombinant PGRN ameliorated the pathology and reduced the histological score in both DSS and TNBS colitis models. In addition, hematopoietic-derived PGRN was critical for protection against DSS-induced colitis, and lack of PGRN signaling in CD4+ T cells also exacerbated experimental colitis. PGRN-mediated protective effect in colitis was compromised in the absence of IL-10 signaling. In addition, PGRN's effect was also largely lost in the TNFR2-deficient colitis model. Collectively, these findings not only provide the new insight into PGRN's anti-inflammatory action in vivo, but may also present PGRN and its derivatives as novel biological agent for treating IBD. Nature Publishing Group 2014-11-12 /pmc/articles/PMC4228332/ /pubmed/25387791 http://dx.doi.org/10.1038/srep07023 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Wei, Fanhua Zhang, Yuying Jian, Jinlong Mundra, Jyoti Joshi Tian, Qingyun Lin, Jiqiang Lafaille, Juan Jose Tang, Wei Zhao, Weiming Yu, Xiuping Liu, Chuan-Ju PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title | PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title_full | PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title_fullStr | PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title_full_unstemmed | PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title_short | PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner |
title_sort | pgrn protects against colitis progression in mice in an il-10 and tnfr2 dependent manner |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228332/ https://www.ncbi.nlm.nih.gov/pubmed/25387791 http://dx.doi.org/10.1038/srep07023 |
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