Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease
Copyright: 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 public domain dedication..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
PloS one - 18(2023), 2 vom: 15., Seite e0282227 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakamura, Hiroyuki [VerfasserIn] |
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| Links: |
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| Themen: |
4QWG6N8QKH |
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| Anmerkungen: |
Date Completed 27.02.2023 Date Revised 26.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0282227 |
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NLM353278831 |
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| 100 | 1 | |a Nakamura, Hiroyuki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease |
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| 520 | |a 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 | ||
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| 650 | 7 | |a Chloroquine |2 NLM | |
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| 700 | 1 | |a Ji, Youngmi |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Changyu |e verfasserin |4 aut | |
| 700 | 1 | |a Afione, Sandra A |e verfasserin |4 aut | |
| 700 | 1 | |a Warner, Blake M |e verfasserin |4 aut | |
| 700 | 1 | |a Oliveira, Fabiola Reis |e verfasserin |4 aut | |
| 700 | 1 | |a Motta, Ana Carolina F |e verfasserin |4 aut | |
| 700 | 1 | |a Rocha, Eduardo M |e verfasserin |4 aut | |
| 700 | 1 | |a Noguchi, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Atsumi, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Chiorini, John A |e verfasserin |4 aut | |
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