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Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway
Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppresso...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246483/ https://www.ncbi.nlm.nih.gov/pubmed/32349250 http://dx.doi.org/10.3390/ijms21093073 |
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author | Al-Araimi, Amna Al Kharusi, Amira Bani Oraba, Asma Al-Maney, Matar M Al Sinawi, Shadia Al-Haddabi, Ibrahim Zadjali, Fahad |
author_facet | Al-Araimi, Amna Al Kharusi, Amira Bani Oraba, Asma Al-Maney, Matar M Al Sinawi, Shadia Al-Haddabi, Ibrahim Zadjali, Fahad |
author_sort | Al-Araimi, Amna |
collection | PubMed |
description | Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2−/−) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2−/− mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 β (IL1-β). At recovery time point, SOCS2−/− showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta β1 (TGF-β1) receptors were significantly lower in SOCS2−/− mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2−/− mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFβ-mothers against the decapentaplegic homolog (Smad) pathway. |
format | Online Article Text |
id | pubmed-7246483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72464832020-06-11 Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway Al-Araimi, Amna Al Kharusi, Amira Bani Oraba, Asma Al-Maney, Matar M Al Sinawi, Shadia Al-Haddabi, Ibrahim Zadjali, Fahad Int J Mol Sci Article Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2−/−) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2−/− mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 β (IL1-β). At recovery time point, SOCS2−/− showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta β1 (TGF-β1) receptors were significantly lower in SOCS2−/− mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2−/− mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFβ-mothers against the decapentaplegic homolog (Smad) pathway. MDPI 2020-04-27 /pmc/articles/PMC7246483/ /pubmed/32349250 http://dx.doi.org/10.3390/ijms21093073 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Al-Araimi, Amna Al Kharusi, Amira Bani Oraba, Asma Al-Maney, Matar M Al Sinawi, Shadia Al-Haddabi, Ibrahim Zadjali, Fahad Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title | Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title_full | Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title_fullStr | Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title_full_unstemmed | Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title_short | Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFβ Pathway |
title_sort | deletion of socs2 reduces post-colitis fibrosis via alteration of the tgfβ pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246483/ https://www.ncbi.nlm.nih.gov/pubmed/32349250 http://dx.doi.org/10.3390/ijms21093073 |
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