Examinando por Autor "González, M."
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Ítem A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis(Nature Publishing Group, 2017-12) Díaz-Jiménez, D.; Núñez, L.; De La Fuente, M.; Dubois-Camacho, K.; Sepúlveda, H.; Montecino, M.; Torres-Riquelme, A.; García-González, P.; Chnaiderman, J.; Vossenkamper, A.; MacDonald, T.T.; Simian, D.; González, M.; Cidlowski, J.A.; Quera, R.; Hermoso, M.A.The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression. Serum ST2 levels and genetic variants in the IL1RL1 distal promoter were examined by ELISA and PCR sequencing in UC patients receiving corticosteroids. Glucocorticoid-mediated ST2 production was evaluated in intestinal mucosa cultures. Molecular regulation of glucocorticoid-mediated ST2 was assessed by RT-qPCR, ChIP assay and luciferase reporter assay. Dexamethasone effect on ST2 transcript expression was analyzed in leukocytes and related to IL1RL1 variants. Sequencing of a distal IL1RL1 promoter region demonstrated that SNPs rs6543115(C) and rs6543116(A) are associated with increased sST2 in UC patients on corticosteroids. Dexamethasone up-regulated sST2 transcription through interaction with the glucocorticoid-response element (GRE) carrying rs6543115(C) variant. Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression.Ítem Genome sequencing and transcriptomic analysis of the Andean killifish Orestias ascotanensis reveals adaptation to high-altitude aquatic life(Elsevier, 2022-01) Di Genova, A.; Nardocci, G.; Maldonado-Agurto, R.; Hodar, Ch.; Valdivieso, C.; Valdivieso, C.; Morales, P.; Gajardo, F.; Marina, R.; Gutiérrez, R.; Orellana, A.; Cambiazo, V.; Cambiazo, V.; González, M.; Glavic, A.; Mendez, M.; Maass, A.; Allende, M.; Montecino, M.Orestias ascotanensis (Cyprinodontidae) is a teleost pupfish endemic to springs feeding into the Ascotan saltpan in the Chilean Altiplano (3,700 m.a.s.l.) and represents an opportunity to study adaptations to high-altitude aquatic environments. We have de novo assembled the genome of O. ascotanensis at high coverage. Comparative analysis of the O. ascotanensis genome showed an overall process of contraction, including loss of genes related to G-protein signaling, chemotaxis and signal transduction, while there was expansion of gene families associated with microtubule-based movement and protein ubiquitination. We identified 818 genes under positive selection, many of which are involved in DNA repair. Additionally, we identified novel and conserved microRNAs expressed in O. ascotanensis and its closely-related species, Orestias gloriae. Our analysis suggests that positive selection and expansion of genes that preserve genome stability are a potential adaptive mechanism to cope with the increased solar UV radiation to which high-altitude animals are exposed to.