title: X-linked ectodermal dysplasia receptor (XEDAR) gene silencing prevents caspase-3-mediated apoptosis in Sjögren's syndrome.
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.
authors.affiliation: Department 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.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sisto
authors.affiliation: Department 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.
authors.forename: Loredana
authors.initials: L
authors.lastname: Lorusso
authors.affiliation: Department 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.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lisi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D053331:Ectodysplasins / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053340:Xedar Receptor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C506018:EDA protein, human; C506011:EDA2R protein, human; D053331:Ectodysplasins; D034741:RNA, Small Interfering; D053340:Xedar Receptor; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Caspase-3; Ectodysplasin-A2; Sjögren’s syndrome; XEDAR