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BMC Syst Biol. 2017 Mar 1;11(1):31. doi: 10.1186/s12918-017-0411-7.

Systems biology combining human- and animal-data miRNA and mRNA data identifies new targets in ureteropelvic junction obstruction.

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Metabolic and Cardiovascular Diseases-I2MC, 1 avenue Jean Poulhès, B.P. 84225, 31432, Toulouse Cedex 4, France.
2
Université Toulouse III Paul-Sabatier, Toulouse, France.
3
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
4
Department of Molecular Medicine, Université Laval, Québec, Canada.
5
Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec, Canada.
6
HybridStat Predictive Analytics, Aiolou 19, 10551, Athens, Greece.
7
Institute of Molecular Biology and Genetics, Biomedical Sciences Research Center 'Alexander Fleming', Fleming 34, 16672, Vari, Greece.
8
Service de Néphrologie-Médecine Interne-Hypertension Pédiatrique, CHU Toulouse, Hôpital des Enfants, 31059, Toulouse, France.
9
Centre De Référence des Maladies Rénales Rares du Sud Ouest (SORARE), 31059, Toulouse, France.
10
Unité de recherche clinique pédiatrique, Module plurithémathique pédiatrique du Centre d'Investigation Clinique Toulouse 1436 Hôpital des enfants 330 avenue de grande bretagne, 31059, Toulouse, France.
11
DéTROI-Inserm U1188-Université de La Réunion, Diabète athérothrombose Thérapies Réunion Océan Indien, CYROI, 2, rue Maxime Rivière, 97490, Sainte Clotilde, La Réunion, France.
12
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Metabolic and Cardiovascular Diseases-I2MC, 1 avenue Jean Poulhès, B.P. 84225, 31432, Toulouse Cedex 4, France. joost-peter.schanstra@inserm.fr.
13
Université Toulouse III Paul-Sabatier, Toulouse, France. joost-peter.schanstra@inserm.fr.
14
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Metabolic and Cardiovascular Diseases-I2MC, 1 avenue Jean Poulhès, B.P. 84225, 31432, Toulouse Cedex 4, France. julie.klein@inserm.fr.
15
Université Toulouse III Paul-Sabatier, Toulouse, France. julie.klein@inserm.fr.

Abstract

BACKGROUND:

Although renal fibrosis and inflammation have shown to be involved in the pathophysiology of obstructive nephropathies, molecular mechanisms underlying evolution of these processes remain undetermined. In an attempt towards improved understanding of obstructive nephropathy and improved translatability of the results to clinical practice we have developed a systems biology approach combining omics data of both human and mouse obstructive nephropathy.

RESULTS:

We have studied in parallel the urinary miRNome of infants with ureteropelvic junction obstruction and the kidney tissue miRNome and transcriptome of the corresponding neonatal partial unilateral ureteral obstruction (UUO) mouse model. Several hundreds of miRNAs and mRNAs displayed changed abundance during disease. Combination of miRNAs in both species and associated mRNAs let to the prioritization of five miRNAs and 35 mRNAs associated to disease. In vitro and in vivo validation identified consistent dysregulation of let-7a-5p and miR-29-3p and new potential targets, E3 ubiquitin-protein ligase (DTX4) and neuron navigator 1 (NAV1), potentially involved in fibrotic processes, in obstructive nephropathy in both human and mice that would not be identified otherwise.

CONCLUSIONS:

Our study is the first to correlate a mouse model of neonatal partial UUO with human UPJ obstruction in a comprehensive systems biology analysis. Our data revealed let-7a and miR-29b as molecules potentially involved in the development of fibrosis in UPJ obstruction via the control of DTX4 in both man and mice that would not be identified otherwise.

KEYWORDS:

DTX4 and NAV1; Microarrays; Obstructive nephropathy; let-7a-5p and miR-29b-3p; miRNAs/microRNAs

PMID:
28249581
PMCID:
PMC5333413
DOI:
10.1186/s12918-017-0411-7
[Indexed for MEDLINE]
Free PMC Article

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