Increased SGK1 activity potentiates mineralocorticoid/NaCl-induced kidney injury

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buir.contributor.authorKeskus, Ayşe Gökçe
buir.contributor.authorKonu, Özlen
buir.contributor.orcidKeskus, Ayşe Gökçe|0000-0002-3934-8587
dc.citation.epageF643en_US
dc.citation.issueNumber4en_US
dc.citation.spageF628en_US
dc.citation.volumeNumber320en_US
dc.contributor.authorSierra-Ramos, Catalina
dc.contributor.authorVelazquez-Garcia, Silvia
dc.contributor.authorKeskus, Ayşe Gökçe
dc.contributor.authorVastola-Mascolo, Arianna
dc.contributor.authorRodríguez-Rodríguez, Ana E.
dc.contributor.authorLuis-Lima, Sergio
dc.contributor.authorHernández, Guadalberto
dc.contributor.authorNavarro-González, Juan F.
dc.contributor.authorPorrini, Esteban
dc.contributor.authorKonu, Özlen
dc.contributor.authorAlvarez de la Rosa, Diego
dc.date.accessioned2022-02-08T13:14:10Z
dc.date.available2022-02-08T13:14:10Z
dc.date.issued2021-04-08
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractSerum and glucocorticoid-regulated kinase 1 (SGK1) stimulates aldosterone-dependent renal Na reabsorption and modulates blood pressure. In addition, genetic ablation or pharmacological inhibition of SGK1 limits the development of kidney inflammation and fibrosis in response to excess mineralocorticoid signaling. In this work, we tested the hypothesis that a systemic increase in SGK1 activity would potentiate mineralocorticoid/salt-induced hypertension and kidney injury. To that end, we used a transgenic mouse model with increased SGK1 activity. Mineralocorticoid/salt-induced hypertension and kidney damage was induced by unilateral nephrectomy and treatment with deoxycorticosterone acetate and NaCl in the drinking water for 6 wk. Our results show that although SGK1 activation did not induce significantly higher blood pressure, it produced a mild increase in glomerular filtration rate, increased albuminuria, and exacerbated glomerular hypertrophy and fibrosis. Transcriptomic analysis showed that extracellular matrix-and immune response-related terms were enriched in the downregulated and upregulated genes, respectively, in transgenic mice. In conclusion, we propose that systemically increased SGK1 activity is a risk factor for the development of mineralocorticoid-dependent kidney injury in the context of low renal mass and independently of blood pressure. NEW and NOTEWORTHY Increased activity of the protein kinase serum and glucocorticoid-regulated kinase 1 may be a risk factor for accelerated renal damage. Serum and glucocorticoid-regulated kinase 1 expression could be a marker for the rapid progression toward chronic kidney disease and a potential therapeutic target to slow down the process. © 2021 American Physiological Society. All rights reserved.en_US
dc.identifier.doi10.1152/ajprenal.00505.2020en_US
dc.identifier.eissn1522-1466
dc.identifier.issn1931-857X
dc.identifier.urihttp://hdl.handle.net/11693/77137
dc.language.isoEnglishen_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.isversionofhttps://doi.org/10.1152/ajprenal.00505.2020en_US
dc.source.titleAmerican Journal of Physiology: Renal Physiologyen_US
dc.subjectAldosteroneen_US
dc.subjectChronic kidney diseaseen_US
dc.subjectFibrosisen_US
dc.subjectMineralocorticoid receptoren_US
dc.subjectSerum and glucocorticoid-regulated kinase 1en_US
dc.titleIncreased SGK1 activity potentiates mineralocorticoid/NaCl-induced kidney injuryen_US
dc.typeArticleen_US

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Department of Molecular Biology and Genetics
Institute of Materials Science and Nanotechnology (UNAM)