MicroRNAs expression profile and reconstruction of gene regulatory networks involved in different periods of renal ontogenesis of animals that suffered gestational protein restriction

• Grant number: 15/15148-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): November 01, 2015
• Effective date (End): February 01, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Patrícia Aline Boer
• Grantee: Letícia de Barros Sene
• Supervisor: Tao Chen
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Research place: National Center for Toxicological Research (NCTR), United States
• Associated to the scholarship: 12/18492-4 - 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, BP.DR

Abstract

Protein-calorie malnutrition and high blood pressure are worldwide public health problems. Epidemiologic studies in different population groups, as well as experimental findings indicate that intrauterine undernutritional "program" the development of hypertension and coronary heart disease in adult rats. From these results it appears that g protein deprivation during gestacional period of nephrogenesis causes a reduction in the number of glomeruli at birth. Thus, a predisposition to hypertension can be determined, at least in part, by abnormal kidney development. 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 compromises nephrogenesis process. Recent studies show that the number of stem cells present in the mesenchymal cap (CM), around of the ureteral bud tip, determines the number of nephrons to be formed. Recently, it was demonstrated that the loss of miRNAs in progenitor cells of the nephron results in premature depletion of this population in parallel to increased apoptosis and the expression of pro-apoptotic protein Bim.The hypothesis of this study is that fetal exposure to maternal glucocorticoids, which occurs in the gestational protein restriction model, can cause depletion and early maturation of progenitor stem cells from CM, and through the characteristic profile of miRNA expression, we will possibly identify networks regulation and molecular pathways involved in fewer nephrons found in this model. In this context, the internship in the laboratory of Dr. Tao Chen aims to analyze: 1) the profile of miRNA expression in different periods of renal ontogenesis in a protein restriction model, 2) the genetic regulatory networks inferred from expression data miRNAs. The results obtained during this stage will be essential to guide the next steps for biological validation of the role of these miRNAs in renal development of offspring that suffered gestational protein restriction, and we intend to analyze the networks regulated in this condition using RT-qPCR, western blot and immunohistochemistry. (AU)