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SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease
BACKGROUND: Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. METHODS: Enzyme linked immunosorbe...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811794/ https://www.ncbi.nlm.nih.gov/pubmed/36600293 http://dx.doi.org/10.1186/s13052-022-01401-8 |
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author | Wen, Zhengwang Xia, Yuhan Zhang, Yingying He, Yuxi Niu, Chao Wu, Rongzhou Zhang, Chunxiang Jia, Chang Rong, Xing Chu, Maoping |
author_facet | Wen, Zhengwang Xia, Yuhan Zhang, Yingying He, Yuxi Niu, Chao Wu, Rongzhou Zhang, Chunxiang Jia, Chang Rong, Xing Chu, Maoping |
author_sort | Wen, Zhengwang |
collection | PubMed |
description | BACKGROUND: Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation. RESULTS: In this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. CONCLUSION: Our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD. |
format | Online Article Text |
id | pubmed-9811794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98117942023-01-05 SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease Wen, Zhengwang Xia, Yuhan Zhang, Yingying He, Yuxi Niu, Chao Wu, Rongzhou Zhang, Chunxiang Jia, Chang Rong, Xing Chu, Maoping Ital J Pediatr Research BACKGROUND: Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation. RESULTS: In this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. CONCLUSION: Our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD. BioMed Central 2023-01-04 /pmc/articles/PMC9811794/ /pubmed/36600293 http://dx.doi.org/10.1186/s13052-022-01401-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wen, Zhengwang Xia, Yuhan Zhang, Yingying He, Yuxi Niu, Chao Wu, Rongzhou Zhang, Chunxiang Jia, Chang Rong, Xing Chu, Maoping SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title | SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title_full | SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title_fullStr | SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title_full_unstemmed | SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title_short | SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease |
title_sort | sigirr-caspase-8 signaling mediates endothelial apoptosis in kawasaki disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811794/ https://www.ncbi.nlm.nih.gov/pubmed/36600293 http://dx.doi.org/10.1186/s13052-022-01401-8 |
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