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Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease
Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren’s disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevate...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949663/ https://www.ncbi.nlm.nih.gov/pubmed/36821638 http://dx.doi.org/10.1371/journal.pone.0282227 |
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author | Nakamura, Hiroyuki Tanaka, Tsutomu Ji, Youngmi Zheng, Changyu Afione, Sandra A. Warner, Blake M. Oliveira, Fabiola Reis Motta, Ana Carolina F. Rocha, Eduardo M. Noguchi, Masayuki Atsumi, Tatsuya Chiorini, John A. |
author_facet | Nakamura, Hiroyuki Tanaka, Tsutomu Ji, Youngmi Zheng, Changyu Afione, Sandra A. Warner, Blake M. Oliveira, Fabiola Reis Motta, Ana Carolina F. Rocha, Eduardo M. Noguchi, Masayuki Atsumi, Tatsuya Chiorini, John A. |
author_sort | Nakamura, Hiroyuki |
collection | PubMed |
description | Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren’s disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, in vitro and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high LAMP3 mRNA expression in minor salivary glands and those with LAMP3 mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high LAMP3 expression compared those with normal LAMP3 expression. Taken together, these findings suggested that by determining salivary gland LAMP3 mRNA level, a patient’s response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD. |
format | Online Article Text |
id | pubmed-9949663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99496632023-02-24 Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease Nakamura, Hiroyuki Tanaka, Tsutomu Ji, Youngmi Zheng, Changyu Afione, Sandra A. Warner, Blake M. Oliveira, Fabiola Reis Motta, Ana Carolina F. Rocha, Eduardo M. Noguchi, Masayuki Atsumi, Tatsuya Chiorini, John A. PLoS One Research Article Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren’s disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, in vitro and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high LAMP3 mRNA expression in minor salivary glands and those with LAMP3 mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high LAMP3 expression compared those with normal LAMP3 expression. Taken together, these findings suggested that by determining salivary gland LAMP3 mRNA level, a patient’s response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD. Public Library of Science 2023-02-23 /pmc/articles/PMC9949663/ /pubmed/36821638 http://dx.doi.org/10.1371/journal.pone.0282227 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Nakamura, Hiroyuki Tanaka, Tsutomu Ji, Youngmi Zheng, Changyu Afione, Sandra A. Warner, Blake M. Oliveira, Fabiola Reis Motta, Ana Carolina F. Rocha, Eduardo M. Noguchi, Masayuki Atsumi, Tatsuya Chiorini, John A. Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title | Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title_full | Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title_fullStr | Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title_full_unstemmed | Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title_short | Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren’s disease |
title_sort | salivary gland lamp3 mrna expression is a possible predictive marker in the response to hydroxychloroquine in sjögren’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949663/ https://www.ncbi.nlm.nih.gov/pubmed/36821638 http://dx.doi.org/10.1371/journal.pone.0282227 |
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