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Comparative study of the effects of protein restriction in utero and dexamethasone in vitro exposure during nephrogenesis: assessment of gene expression, of miRNAs, protein, and morphometric in metanephric mesenchyme

Grant number: 12/18492-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2014
Effective date (End): June 01, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Patrícia Aline Boer
Grantee:Letícia de Barros Sene
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):15/15148-9 - MicroRNAs expression profile and reconstruction of gene regulatory networks involved in different periods of renal ontogenesis of animals that suffered gestational protein restriction, BE.EP.DR


Both the protein-calorie malnutrition and hypertension represent global problems of public health. Epidemiologic studies in populations, as well as experimental results indicate that intrauterine nutritional conditions "program" the development of hypertension and coronary heart disease in adults. From these results has been showed that protein deprivation during pregnancy, an active period of nephrogenesis, causes reduction in the glomeruli number at birth. Thus, the predisposition to hypertension can be determined at least in part, by abnormal development of kidney. One of the factors involved in the genesis of fetal programming is the increased fetus exposure to maternal glucocorticoids. However it is not known whether this mechanism is also involved and undertakes the process of nephrogenesis. Recent studies show that the number of mesenchymal cap (CM) stem cells, around the edge of the shoot of the ureter, determines the final number of nephrons. The objectives of this project are: 1) assess the CM area and the rates of cells death and proliferation in CM, 2) gene and miRNAs expression; 3) number of positive cells for proteins controlling cell cycle, Bim protein and stem cells markers in the CM of the offspring of rats subjected to protein restriction during pregnancy, compared to their controls, at different periods of renal ontogenesis. Will also be checked the same parameters in cultured metanefros exposed to dexamethasone (DEX) mimicking fetal corticosteroids high concentration that has been verified in the gestational protein restriction models. The studies aim to associate both morphometric profile and gene expression to the nephron reduction observed in this model.

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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)
SENE, LETICIA DE BARROS; LAMANA, GABRIELA LEME; VIEIRA, ANDRE SCHWAMBACH; SCARANO, WELLERSON RODRIGO; ROCHA GONTIJO, JOSE ANTONIO; BOER, PATRICIA ALINE. estational Low Protein Diet Modulation on miRNA Transcriptome and Its Target During Fetal and Breastfeeding Nephrogenesi. FRONTIERS IN PHYSIOLOGY, v. 12, . (13/12486-5, 14/50938-8, 12/18492-4)
GOMES, JULIA SEVA; SENE, LETICIA BARROS; LAMANA, GABRIELA LEME; BOER, PATRICIA ALINE; GONTIJO, JOSE ANTONIO ROCHA. Impact of maternal protein restriction on Hypoxia-Inducible Factor (HIF) expression in male fetal kidney development. PLoS One, v. 18, n. 5, p. 18-pg., . (13/12486-5, 14/50938-8, 12/18492-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SENE, Letícia de Barros. MRNAs, miRNAs, and regulatory protein expression nephrogenesis in rats programmed by protein restriction in utero. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.

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