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CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38 Pathway in Macrophages
OBJECTIVE: C1q/TNF-related proteins 1 (CTRP1) is a recently identified adiponectin associated with obesity-linked disorders and adverse cardiovascular events. The effect of CTRP1 on cardiac fibrosis has not yet been fully elucidated; thus, we aimed to explore this association. MATERIALS AND METHODS:...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royan Institute
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790075/ https://www.ncbi.nlm.nih.gov/pubmed/36527345 http://dx.doi.org/10.22074/CELLJ.2022.557327.1043 |
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author | Li, Chenyu Ying, Shaozhen Wu, Xiaolin Zhu, Tongjian Zhou, Qing Zhang, Yue Liu, Yongsheng Zhu, Rui Hu, He |
author_facet | Li, Chenyu Ying, Shaozhen Wu, Xiaolin Zhu, Tongjian Zhou, Qing Zhang, Yue Liu, Yongsheng Zhu, Rui Hu, He |
author_sort | Li, Chenyu |
collection | PubMed |
description | OBJECTIVE: C1q/TNF-related proteins 1 (CTRP1) is a recently identified adiponectin associated with obesity-linked disorders and adverse cardiovascular events. The effect of CTRP1 on cardiac fibrosis has not yet been fully elucidated; thus, we aimed to explore this association. MATERIALS AND METHODS: In this experimental study, a mouse model of cardiac fibrosis was established by administering isoproterenol (ISO) (subcutaneously injecting 10 mg/kg/day for 3 days and then 5 mg/kg/day for 11 days). Mice were also injected with recombinant CTRP1 protein (200 μg/kg) 14 days after the final ISO administration. Adult mouse fibroblasts were isolated and stimulated with transforming growth factor (TGF) β1, followed by treatment with recombinant CTRP1. Primary bone marrow-derived macrophages were isolated from C57BL/6J mice and treated with recombinant CTRP1 as well. RESULTS: CTRP1 level was increased in mouse plasma and heart tissue 2 weeks after ISO injection. Our findings indicated that recombinant CTRP1 injection aggravated ISO-induced cardiac fibrosis and dysfunction. However, recombinant CTRP1 did not alter TGFβ1-induced fibroblast proliferation and activation or collagen transcription. Recombinant CTRP1 exacerbated ISO-induced macrophage infiltration and inflammatory response. We determined that macrophages treated with recombinant CTRP1 showed increased pro-inflammatory cytokine release. Fibroblasts co-cultured with macrophages treated with recombinant CTRP1 showed increased proliferation and collagen transcription. We also found that CTRP1 upregulated the NADPH oxidase 2 (NOX2)/p38 pathway in macrophages. When we inhibited p38 signaling, the pro-inflammatory effect of CTRP1 on macrophages was counteracted. Fibroblasts co-cultured with macrophages treated with a p38 inhibitor also showed limited proliferation and collagen transcription. CONCLUSION: Cardiac fibrosis was aggravated with the activation of the NOX2/p38 pathway in macrophages after CTRP1 treatment. |
format | Online Article Text |
id | pubmed-9790075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Royan Institute |
record_format | MEDLINE/PubMed |
spelling | pubmed-97900752023-01-03 CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38 Pathway in Macrophages Li, Chenyu Ying, Shaozhen Wu, Xiaolin Zhu, Tongjian Zhou, Qing Zhang, Yue Liu, Yongsheng Zhu, Rui Hu, He Cell J Original Article OBJECTIVE: C1q/TNF-related proteins 1 (CTRP1) is a recently identified adiponectin associated with obesity-linked disorders and adverse cardiovascular events. The effect of CTRP1 on cardiac fibrosis has not yet been fully elucidated; thus, we aimed to explore this association. MATERIALS AND METHODS: In this experimental study, a mouse model of cardiac fibrosis was established by administering isoproterenol (ISO) (subcutaneously injecting 10 mg/kg/day for 3 days and then 5 mg/kg/day for 11 days). Mice were also injected with recombinant CTRP1 protein (200 μg/kg) 14 days after the final ISO administration. Adult mouse fibroblasts were isolated and stimulated with transforming growth factor (TGF) β1, followed by treatment with recombinant CTRP1. Primary bone marrow-derived macrophages were isolated from C57BL/6J mice and treated with recombinant CTRP1 as well. RESULTS: CTRP1 level was increased in mouse plasma and heart tissue 2 weeks after ISO injection. Our findings indicated that recombinant CTRP1 injection aggravated ISO-induced cardiac fibrosis and dysfunction. However, recombinant CTRP1 did not alter TGFβ1-induced fibroblast proliferation and activation or collagen transcription. Recombinant CTRP1 exacerbated ISO-induced macrophage infiltration and inflammatory response. We determined that macrophages treated with recombinant CTRP1 showed increased pro-inflammatory cytokine release. Fibroblasts co-cultured with macrophages treated with recombinant CTRP1 showed increased proliferation and collagen transcription. We also found that CTRP1 upregulated the NADPH oxidase 2 (NOX2)/p38 pathway in macrophages. When we inhibited p38 signaling, the pro-inflammatory effect of CTRP1 on macrophages was counteracted. Fibroblasts co-cultured with macrophages treated with a p38 inhibitor also showed limited proliferation and collagen transcription. CONCLUSION: Cardiac fibrosis was aggravated with the activation of the NOX2/p38 pathway in macrophages after CTRP1 treatment. Royan Institute 2022-12 2022-12-12 /pmc/articles/PMC9790075/ /pubmed/36527345 http://dx.doi.org/10.22074/CELLJ.2022.557327.1043 Text en Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited. https://creativecommons.org/licenses/by-nc/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Li, Chenyu Ying, Shaozhen Wu, Xiaolin Zhu, Tongjian Zhou, Qing Zhang, Yue Liu, Yongsheng Zhu, Rui Hu, He CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38 Pathway in Macrophages |
title | CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38
Pathway in Macrophages |
title_full | CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38
Pathway in Macrophages |
title_fullStr | CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38
Pathway in Macrophages |
title_full_unstemmed | CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38
Pathway in Macrophages |
title_short | CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38
Pathway in Macrophages |
title_sort | ctrp1 aggravates cardiac fibrosis by regulating the nox2/p38
pathway in macrophages |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790075/ https://www.ncbi.nlm.nih.gov/pubmed/36527345 http://dx.doi.org/10.22074/CELLJ.2022.557327.1043 |
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