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Coordinated local RNA overexpression of complement induced by interferon gamma in myositis
Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that compleme...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899209/ https://www.ncbi.nlm.nih.gov/pubmed/36739295 http://dx.doi.org/10.1038/s41598-023-28838-z |
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author | Casal-Dominguez, Maria Pinal-Fernandez, Iago Pak, Katherine Muñoz-Braceras, Sandra Milisenda, Jose C. Torres-Ruiz, Jiram Dell′Orso, Stefania Naz, Faiza Gutierrez-Cruz, Gustavo Duque-Jaimez, Yaiza Matas-Garcia, Ana Valls-Roca, Laura Garrabou, Gloria Trallero-Araguas, Ernesto Walitt, Brian Christopher-Stine, Lisa Lloyd, Thomas E. Paik, Julie J. Albayda, Jemima Corse, Andrea Grau, Josep Maria Selva-O’Callaghan, Albert Mammen, Andrew L. |
author_facet | Casal-Dominguez, Maria Pinal-Fernandez, Iago Pak, Katherine Muñoz-Braceras, Sandra Milisenda, Jose C. Torres-Ruiz, Jiram Dell′Orso, Stefania Naz, Faiza Gutierrez-Cruz, Gustavo Duque-Jaimez, Yaiza Matas-Garcia, Ana Valls-Roca, Laura Garrabou, Gloria Trallero-Araguas, Ernesto Walitt, Brian Christopher-Stine, Lisa Lloyd, Thomas E. Paik, Julie J. Albayda, Jemima Corse, Andrea Grau, Josep Maria Selva-O’Callaghan, Albert Mammen, Andrew L. |
author_sort | Casal-Dominguez, Maria |
collection | PubMed |
description | Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that complement genes are locally overexpressed and correlate with markers of myositis disease activity, including the expression of interferon-gamma (IFNγ)-induced genes. Single cell and single nuclei RNAseq analyses showed that most local expression of complement genes occurs in macrophages, fibroblasts, and satellite cells, with each cell type expressing different sets of complement genes. Biopsies from immune-mediated necrotizing myopathy patients, who have the lowest levels of IFNγ-induced genes, also had the lowest complement gene expression levels. Furthermore, data from cultured human cells showed that IFNγ upregulates complement expression in macrophages, fibroblasts, and muscle cells. Taken together, our results suggest that in myositis muscle, IFNγ coordinates the local overexpression of complement genes that occurs in several cell types. |
format | Online Article Text |
id | pubmed-9899209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98992092023-02-06 Coordinated local RNA overexpression of complement induced by interferon gamma in myositis Casal-Dominguez, Maria Pinal-Fernandez, Iago Pak, Katherine Muñoz-Braceras, Sandra Milisenda, Jose C. Torres-Ruiz, Jiram Dell′Orso, Stefania Naz, Faiza Gutierrez-Cruz, Gustavo Duque-Jaimez, Yaiza Matas-Garcia, Ana Valls-Roca, Laura Garrabou, Gloria Trallero-Araguas, Ernesto Walitt, Brian Christopher-Stine, Lisa Lloyd, Thomas E. Paik, Julie J. Albayda, Jemima Corse, Andrea Grau, Josep Maria Selva-O’Callaghan, Albert Mammen, Andrew L. Sci Rep Article Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that complement genes are locally overexpressed and correlate with markers of myositis disease activity, including the expression of interferon-gamma (IFNγ)-induced genes. Single cell and single nuclei RNAseq analyses showed that most local expression of complement genes occurs in macrophages, fibroblasts, and satellite cells, with each cell type expressing different sets of complement genes. Biopsies from immune-mediated necrotizing myopathy patients, who have the lowest levels of IFNγ-induced genes, also had the lowest complement gene expression levels. Furthermore, data from cultured human cells showed that IFNγ upregulates complement expression in macrophages, fibroblasts, and muscle cells. Taken together, our results suggest that in myositis muscle, IFNγ coordinates the local overexpression of complement genes that occurs in several cell types. Nature Publishing Group UK 2023-02-04 /pmc/articles/PMC9899209/ /pubmed/36739295 http://dx.doi.org/10.1038/s41598-023-28838-z Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Casal-Dominguez, Maria Pinal-Fernandez, Iago Pak, Katherine Muñoz-Braceras, Sandra Milisenda, Jose C. Torres-Ruiz, Jiram Dell′Orso, Stefania Naz, Faiza Gutierrez-Cruz, Gustavo Duque-Jaimez, Yaiza Matas-Garcia, Ana Valls-Roca, Laura Garrabou, Gloria Trallero-Araguas, Ernesto Walitt, Brian Christopher-Stine, Lisa Lloyd, Thomas E. Paik, Julie J. Albayda, Jemima Corse, Andrea Grau, Josep Maria Selva-O’Callaghan, Albert Mammen, Andrew L. Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title | Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title_full | Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title_fullStr | Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title_full_unstemmed | Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title_short | Coordinated local RNA overexpression of complement induced by interferon gamma in myositis |
title_sort | coordinated local rna overexpression of complement induced by interferon gamma in myositis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899209/ https://www.ncbi.nlm.nih.gov/pubmed/36739295 http://dx.doi.org/10.1038/s41598-023-28838-z |
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