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Published on: September 20, 2024
X-linked ectodermal dysplasia receptor (XEDAR) gene silencing prevents caspase-3-mediated apoptosis in Sjögren's
Margherita Sisto1, Loredana Lorusso2, Sabrina Lisi2
1Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Piazza Giulio Cesare 1, 70124, Bari, Italy. margherita.sisto@uniba.it.
Abstract:
Despite recent advancements in the knowledge of the etiology and pathogenic mechanisms, treatment of the autoimmune disease Sjögren's syndrome (SS) remains mostly empiric and symptom-based, indicating the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the expression and the biological activity of EDA-A2 in human salivary gland epithelial cells (SGEC) from primary Sjögren's syndrome (pSS) patients. We report that EDA-A2 and its receptor XEDAR are overexpressed in pSS SGEC in comparison with healthy individuals and that the EDA-A2/XEDAR system in these cells is involved in the induction of apoptosis via caspases activation. Collectively, our results suggest that EDA-A2/XEDAR system may be a promising agent for the gene therapy of pSS.
Insights
Ectodysplasin-A2 (EDA-A2) and its receptor XEDAR are overexpressed in Sjögren's syndrome salivary cells, promoting apoptosis. This EDA-A2/XEDAR system shows promise for Sjögren's syndrome gene therapy.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Sjögren's syndrome (SS) treatment is largely symptomatic, necessitating novel therapeutic strategies.
- Ectodysplasin-A2 (EDA-A2), a TNF superfamily member, interacts with its receptor XEDAR.
- Understanding the role of EDA-A2/XEDAR in SS pathogenesis is crucial.
Purpose of the Study:
- To investigate the expression and biological activity of EDA-A2 in salivary gland epithelial cells (SGEC) from primary Sjögren's syndrome (pSS) patients.
- To determine the involvement of the EDA-A2/XEDAR system in pSS pathogenesis.
- To evaluate the potential of the EDA-A2/XEDAR system as a therapeutic target for pSS.
Main Methods:
- Analysis of EDA-A2 and XEDAR expression in SGEC from pSS patients and healthy individuals.
- Assessment of the biological activity of the EDA-A2/XEDAR system in pSS SGEC.
- Investigation of apoptosis induction mechanisms, including caspase activation.
Main Results:
- EDA-A2 and XEDAR were found to be overexpressed in pSS SGEC compared to healthy controls.
- The EDA-A2/XEDAR system in pSS SGEC was implicated in inducing apoptosis.
- Caspase activation was identified as a key component in EDA-A2/XEDAR-mediated apoptosis.
Conclusions:
- The EDA-A2/XEDAR system is upregulated in primary Sjögren's syndrome.
- This system plays a role in the apoptotic pathways within salivary gland epithelial cells in pSS.
- The EDA-A2/XEDAR system represents a potential target for gene therapy in Sjögren's syndrome.
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