Comparative transcriptional profiling of renal cortex in rats with inherited stress-induced arterial hypertension and normotensive Wistar Albino Glaxo rats

Abstract

BackgroundThe renal function plays a leading role in long-term control of arterial pressure. The comparative analysis of renal cortex transcriptome in ISIAH rats with inherited stress-induced arterial hypertension and normotensive WAG rats was performed using RNA-Seq approach. The goal of the study was to identify the differentially expressed genes (DEGs) related to hypertension and to detect the pathways contributing to the differences in renal functions in ISIAH and WAG rats.ResultsThe analysis revealed 716 genes differentially expressed in renal cortex of ISIAH and WAG rats, 42 of them were associated with arterial hypertension and regulation of blood pressure (BP). Several Gene Ontology (GO) terms significantly enriched with DEGs suggested the existence of the hormone dependent interstrain differences in renal cortex function. Multiple DEGs were associated with regulation of blood pressure and blood circulation, with the response to stress (including oxidative stress, hypoxia, and fluid shear stress) and its regulation. Several other processes which may contribute to hypertension development in ISIAH rats were: ion transport, regulation of calcium ion transport, homeostatic process, tissue remodeling, immune system process and regulation of immune response.KEGG analysis marked out several pathways significantly enriched with DEGs related to immune system function, to steroid hormone biosynthesis, tryptophan, glutathione, nitrogen, and drug metabolism.ConclusionsThe results of the study provide a basis for identification of potential biomarkers of stress-sensitive hypertension and for further investigation of the mechanisms that affect renal cortex function and hypertension development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0306-9) contains supplementary material, which is available to authorized users.

The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension

“…The upregulation of the podocyte-expressed MIF induces an injury of podocytes and accelerates the progression of glomerulosclerosis [57]. In ISIAH rats, the upregulation of Mif gene was found both in renal cortex [9] and in renal medulla (the current study), and possibly may contribute to development of atherosclerosis as well as to glomerulo- and medullary sclerosis histologically determined earlier [7, 8]. …”

“…In the current study, the PLS regression method, which is commonly used for biomarker selection in metabolomic [36] and gene expression [37] studies, reckoned Ephx2 as one of the genes making the most significant contribution to the inter-strain differences. All this and the increased transcription of Ephx2 found earlier in hypothalamus [38] and renal cortex [9] of ISIAH rats prompt us to consider Ephx2 as a key candidate for further studies of the mechanisms underlying the stress-sensitive hypertension in ISIAH rats. The sEH was already considered as a suitable target for pharmaceutical intervention in the hypertension treatment [39].…”

“…Each group of experimental animals contained 3 rats. Rats were individually caged one week before the measurement of the systolic arterial BP, which was measured indirectly by the tail-cuff method as it was described earlier [9]. The mean systolic arterial BP was 171.7 ± 1.22 mmHg in the experimental group of ISIAH males and 116.33 ± 1.86 mmHg in WAG.…”

“…Recently, using the next-generation RNA sequencing (RNA-Seq) approach, we analyzed the renal cortex transcriptome in ISIAH rats [9]. The results of this study showed that the functioning of the renal cortex in ISIAH rats is based on the changes in transcriptional activity of multiple genes related to different biological processes and metabolic pathways.…”

The papers presented at 7th Young Scientists School “Systems Biology and Bioinformatics” (SBB’15): Introductory Note

“…The paper by Fedoseeva et al titled "Comparative transcriptional profiling of renal cortex in rats with Inherited Stress-Induced Arterial Hypertension and normotensive Wistar Albino Glaxo rats" dissect genetic underpinnings of arterial hypertension, a disease which cannot be explained as progression along a straightforward route [2]. Hence, the entire biochemical network that runs within the renal cortex was considered, with every participating gene classified as either an element in the process imbalanced or otherwise disturbed due to the development of pathology, or as the compensatory change evoked in the processes of an attempt to restore the homeostasis.…”