Structural Characteristics of Renomedullary Interstitial Cells of Hypertensive ISIAH Rats

Filyushina, E. E.; Шмерлинг, М. Д.; Бузуева, И. И.; Lazarev, V. A.; Markel, A. L.; Yakobson, G. S.

doi:10.1007/s10517-013-2164-7

Cited by 9 publications

(5 citation statements)

References 12 publications

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“…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]. …”

Section: Discussionsupporting

confidence: 56%

“…The development of the hypertensive state in ISIAH rats is also accompanied by a hypertrophy of the left ventricle, increase in the wall thickness of the small arteries, and changes in the electrocardiographic pattern [6]. The studies on the kidney histology showed the alterations, which were indicative of an increase in filtration barrier functional load and of processes leading to the development of glomerular [7] and medullary sclerosis in ISIAH rats [8]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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BackgroundThe changes in the renal function leading to a reduction of medullary blood flow can have a great impact on sodium and water homeostasis and on the long-term control of arterial blood pressure. The RNA-Seq approach was used for transcriptome profiling of the renal medulla from hypertensive ISIAH and normotensive WAG rats to uncover the genetic basis of the changes underlying the renal medulla function in the ISIAH rats being a model of the stress-sensitive arterial hypertension and to reveal the genes which possibly may contribute to the alterations in medullary blood flow.ResultsMultiple DEGs specifying the function of renal medulla in ISIAH rats were revealed. The group of DEGs described by Gene Ontology term ‘oxidation reduction’ was the most significantly enriched one. The other groups of DEGs related to response to external stimulus, response to hormone (endogenous) stimulus, response to stress, and homeostatic process provide the molecular basis for integrated responses to homeostasis disturbances in the renal medulla of the ISIAH rats. Several DEGs, which may modulate the renal medulla blood flow, were detected. The reduced transcription of Nos3 pointed to the possible reduction of the blood flow in the renal medulla of ISIAH rats.ConclusionsThe generated data may be useful for comparison with those from different models of hypertension and for identifying the common molecular determinants contributing to disease manifestation, which may be potentially used as new pharmacological targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0462-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Comparative electron microscopic study of glomerular apparatus in 6-month old ISIAH and Wistar rats showed hypertrophy of renal corpuscles in hypertensive kidney, accompanied by multiple structural changes such as capillary narrowing or dilation, endothelial flattening, podocyte hypertrophy and flattening of their cytopodia, thickening of basal lamina, mesangial volume expansion and increase in the number of intercapillary processes of mesangial cells [ 21 ]. Besides, the renal medullary interstitial cells of ISIAH kidneys were characterized by higher numerical density and were enlarged with a higher volume share of their secretory granules [ 22 ]. Complex of these signs suggested a disturbance of glomerular capillary blood circulation and a functional podocyte stress, compensating the microcirculatory disturbances.…”

Section: Resultsmentioning

confidence: 99%

“…Complex of these signs suggested a disturbance of glomerular capillary blood circulation and a functional podocyte stress, compensating the microcirculatory disturbances. Changes in basal membranes and mesangium are indicative of not only increase in filtration barrier functional load, but also of initial stages of glomerular [ 21 ] and renomedullar sclerosis [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

et al. 2015

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BackgroundThe kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight.ResultsSeveral known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males. The knowledge-driven filtering of the list of candidates helped to suggest several positional candidate genes, which may be related to the structural and mass changes in hypertensive ISIAH kidney.In the current study, we showed that all loci found for absolute and relative kidney weight didn't overlap with significant or suggestive loci for arterial blood pressure level. So, the genes differentially expressed in ISIAH and WAG kidneys and located in these QTL regions associated with absolute and relative kidney weight shouldn't substantially influence the BP level in the 6 month-old ISIAH rats. However, in some cases, small effects may be suggested.ConclusionsThe further experimental validation of causative genes and detection of polymorphisms will provide opportunities to advance our understanding of the underlying nature of structural and mass changes in hypertensive ISIAH kidney.

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“…The ISIAH rats also show a number of other characteristic features of hypertensive state: hypertrophy of the left ventricle, increase in the wall thickness of the small arteries, and changes in the electrocardiographic pattern [ 7 ]. ISIAH rats are also characterized by increased kidney mass [ 8 ] and some alterations in kidney histology indicative of increase in filtration barrier functional load and of initial stages of glomerular [ 9 ] and renomedullar sclerosis [ 10 ]. These features, the genetically determined enhanced responsiveness to stressful stimulation, and the predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenocortical (HPA) and sympathoadrenal systems during the disease development let to consider the ISIAH rat strain as an advantageous model of the human stress-sensitive hypertensive state [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Structural Characteristics of Renomedullary Interstitial Cells of Hypertensive ISIAH Rats

Cited by 9 publications

References 12 publications

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

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

Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

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

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