Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.08.191874v1?rss=1 Authors: Catalina Sierra-Ramos, Silvia Velazquez-Garcia, Ayse G. Keskus, Arianna Vastola-Mascolo, Ana E. Rodríguez-Rodríguez, Sergio Luis-Lima, Guadalberto Hernández, Juan F. Navarro-González, Esteban Porrini, Ozlen Konu, Diego Alvarez de la Rosa Abstract: The serum and glucocorticoid-induced 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 signalling. 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 drinking water for six weeks. Our results demonstrate higher systolic blood pressure in treated transgenic mice when compared to wild type counterparts. Transgenic mice showed a mild increase in glomerular filtration rate, increased albuminuria, 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 hypertension and incipient kidney injury in the context of low renal mass. Copy rights belong to original authors. Visit the link for more info