title: Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney.
abstract: Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.
authors.affiliation: Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba, Av. Haya de la Torre 1er Piso, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: César Andrés
authors.initials: CA
authors.lastname: Romero
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Remor
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
authors.affiliation: Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba, Av. Haya de la Torre 1er Piso, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: De Paul
authors.affiliation: Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba, Av. Haya de la Torre 1er Piso, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Alicia Inés
authors.initials: AI
authors.lastname: Torres
authors.affiliation: Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Universidad Nacional de Córdoba, Av. Haya de la Torre 1er Piso, Ciudad Universitaria, 5000, Córdoba, Argentina. mukdsijorge@gmail.com.
authors.forename: Jorge Humberto
authors.initials: JH
authors.lastname: Mukdsi
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis / Q000139:chemically induced; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D017208:Rats, Wistar; D051785:Smad Proteins / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology*
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D051785:Smad Proteins; D014527:Uric Acid; D020170:Caspase 1
keywords: Epithelial-mesenchymal transition; Kidney; Mitochondria; NLRP3/ASC; Smad 2/3; Uric acid