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Title: Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.
Authors: Frejo, Lidia
Requena, Teresa
Okawa, Satoshi
Gallego-Martinez, Alvaro
Martinez-Bueno, Manuel
Aran, Ismael
Batuecas-Caletrio, Angel
Benitez-Rosario, Jesus
Espinosa-Sanchez, Juan M
Fraile-Rodrigo, Jesus José
García-Arumi, Ana María
González-Aguado, Rocío
Marques, Pedro
Martin-Sanz, Eduardo
Perez-Fernandez, Nicolas
Pérez-Vázquez, Paz
Perez-Garrigues, Herminio
Santos-Perez, Sofía
Soto-Varela, Andres
Tapia, Maria C
Trinidad-Ruiz, Gabriel
Del Sol, Antonio
Alarcon Riquelme, Marta E
Lopez-Escamez, Jose A
Keywords: Meniere’s disease;NF-κB signaling;NFKB1;TNFRSF12A;TWEAK/Fn14 pathway;sensorineural hearing loss;vertigo
Issue Date: 13-Dec-2017
Abstract: Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10-09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10-11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.
metadata.dc.identifier.doi: 10.3389/fimmu.2017.01739
ISSN: 1664-3224
Appears in Collections:Producción 2020

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