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Study of aldosterone nongenomic effects: receptor and signaling pathways in the proximal tubule and participation in the kidney injury mechanism


Recently, many researchers believed that aldosterone modulated only the distal nephron ion transport by genomic pathway. However, our recent publications demonstrate genomic and nongenomic effects of aldosterone in proximal tubule (S2 and S3 segments) and the participation of mineralocorticoid receptor (MR) in genomic effects. The receptor and the nongenomic signaling pathways are still unknown, although our recent data indicated that the glucocorticoid receptor (GR) is involved in rapid effects of aldosterone in kidney and a current publication demonstrated that its rapid vascular effects are due to endothelial and vascular smooth muscle GPR30 receptor. This project aims to confirm the participation of GR and/or GPR30 in the aldosterone nongenomics effects on the intracellular calcium concentration ([Ca2+]i) and on the Na+/H+ and H+-ATPase of kidney, in addition to researching the involvement of ERK1 / 2, cAMP, PKC and PLC in the signaling pathways of these effects, using immortalized proximal tubule cells of rats (IRPTC) and S3 segments of proximal tubules isolated from rats as experimental models. Considering the involvement of aldosterone in the pathogenesis of progressive renal dysfunction, will be performed in vivo experiments that allow relating a non-genomic mechanism (activation and expression of EGFR and ERK1/2 in renal tissue) with the establishment of kidney injury, both induced by aldosterone. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LEITE-DELLOVA, DEISE C. A.; SZRIBER, SHIRLEY J.; MERIGHE, GIOVANA K. F.; POLIDORO, JULIANO Z.; REBOUCAS, NANCY A.; OLIVEIRA-SOUZA, MARIA; DE MELLO-AIRES, MARGARIDA. Signaling pathways involved in the rapid biphasic effect of aldosterone on Na+/H(+)exchanger in rat proximal tubule cells. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, v. 182, p. 87-94, SEP 2018. Web of Science Citations: 2.

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