Aquaporins: Unexpected actors in autoimmune diseases

Delporte, Christine; Soyfoo, Muhammad Shahnawaz

doi:10.1016/j.autrev.2022.103131

Cited by 11 publications

(6 citation statements)

References 88 publications

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“…Several lines of evidence associated with our identified enriched genes support this hypothesis. For example, the products of the four most enriched candidate genes, AQP1, ABL2, CHD3, and RELN, participate in inflammatory activation, cell adhesion and migration, wound healing, and organ regeneration [36][37][38][39][40][41]. In addition, they play important roles in the nervous system and are associated with central and periphery neuropathies [39,[42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

Guo,

Li,

et al. 2024

Preprint

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A comprehensive understanding of the genetic predisposition associated with the initiation and development of Sjogren's syndrome (SjS) is imperative. This would not only enrich our knowledge of the pathogenesis underlying this autoimmune disease but also address the long-standing clinical challenges of more timely diagnosis and effective treatment to retain organ function and improve prognosis. In this study, we used whole exome sequencing analysis of 50 patients with SjS to investigate the predisposing variants, genes, and their associated biological functions. Hundreds of predisposing genes were identified, and numerous biological processes and pathways were highlighted; suggesting a heterogeneity of genetic predisposition to SjS. Female patients carrying a greater number of enriched variants tended to have higher levels of serum IgG and corresponding systemic involvement, demonstrating the pivotal role of genetic predisposition in the pathogenesis of SjS. Biological function analysis indicated that a subset of SjS and neuropathies may share a similar genetic predisposition. Our results showed that extracellular matrix-receptor interactions, macrophage-associated biological functions, and motor proteins may play important roles in the pathogenesis of SjS, and macrophage-associated biological functions may be associated with early onset SjS in female patients. Furthermore, the identification of highly enriched variants in the patient cohort provides the possibility of advancing the diagnosis of SjS. In conclusion, our study provides an extensive framework for analysis of the genetic predisposition to SjS which can facilitate further focused and in-depth investigation of the pathogenetic mechanisms of specific genes, biological processes, and pathways; thereby contributing to the pathophysiology, diagnosis, and therapeutics of SjS.

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Section: Discussionmentioning

confidence: 99%

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

Guo,

Li,

et al. 2024

Preprint

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“…Considering these facts, we tested the efficacy of DPSC-Exos in improving the function of SGEC during SS. AQP5 is a key secretory protein that is downregulated in SGEC during SS [ 40 ]. IFN-γ is the inflammatory cytokine released by infiltrated immune cells in the salivary gland that mainly disrupts SGEC survival and functions [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway

Hu,

Chen,

Zhou

et al. 2023

J Transl Med

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Background Restoration of salivary gland function in Sjogren’s syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet. Methods DPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis. Results DPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+ levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER. Conclusions Our results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.

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“…Of the known AQPs, six are expressed in mammalian SGs [ 53 , 54 ]. Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of chronic inflammatory diseases, including SS [ 55 , 56 ]. Indeed, the expression, localization, and function of AQPs have been extensively studied in the SGs of patients affected by SS [ 55 , 56 ].…”

Section: Novel Insights Into the Role Of Aquaporins In The Pathogenes...mentioning

confidence: 99%

“…Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of chronic inflammatory diseases, including SS [ 55 , 56 ]. Indeed, the expression, localization, and function of AQPs have been extensively studied in the SGs of patients affected by SS [ 55 , 56 ]. In SG biopsies from SS patients, AQP1 expression was considerably decreased in myoepithelial cells (MECs) as compared to healthy controls [ 57 ].…”

Section: Novel Insights Into the Role Of Aquaporins In The Pathogenes...mentioning

confidence: 99%

Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren’s Syndrome: Identification of New Targets

Sisto

Ribatti

Lisi

2022

IJMS

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Sjögren’s syndrome (SS) is a systemic autoimmune rheumatic disorder characterized by the lymphocytic infiltration of exocrine glands and the production of autoantibodies to self-antigens. The involvement of the exocrine glands drives the pathognomonic manifestations of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) that define sicca syndrome. To date, the molecular mechanisms mediating pathological salivary gland dysfunction in SS remain to be elucidated, despite extensive studies investigating the underlying cause of this disease, hampering the development of novel therapeutic strategies. Many researchers have identified a multifactorial pathogenesis of SS, including environmental, genetic, neuroendocrine, and immune factors. In this review, we explore the latest developments in understanding the molecular mechanisms involved in the pathogenesis of SS, which have attracted increasing interest in recent years.

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Aquaporins: Unexpected actors in autoimmune diseases

Cited by 11 publications

References 88 publications

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway

Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren’s Syndrome: Identification of New Targets

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