Intrarenal activation of endothelin type B receptors improves kidney oxygenation in type 1 diabetic rats

Franzén, Stephanie; Pihl, Liselotte; Fasching, Angelica; Palm, Fredrik

doi:10.1152/ajprenal.00498.2017

Cited by 6 publications

(3 citation statements)

References 31 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data showed that hypoxia down-regulates ENDRB gene expression and that inhibition of ERN1 signaling leads to up-regulation of this gene. These results conform to data that intrarenal activation of endothelin type B receptors improve kidney oxygenation in type 1 diabetic rats and that pharmacological inhibition and cardiac-specific knockout of endothelin receptor type B lead to cardiac resistance to extreme hypoxia (Franzen et al 2018;Stobdan et al 2018).…”

Section: Discussionsupporting

confidence: 89%

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Minchenko

Tsymbal

Riabovol

et al. 2019

Endocrine Regulations

View full text Add to dashboard Cite

Objective. The aim of the present investigation was to study the effect of hypoxia on the expression of genes encoding endothelin-1 (EDN1) and its cognate receptors (EDNRA and EDNRB) as well as endothelin converting enzyme 1 (ECE1) in U87 glioma cells in response to inhibition of endoplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) for evaluation of their possible significance in the control of glioma growth through ERN1 and hypoxia.Methods. The expression level of EDN1, EDNRA, EDNRB, and ECE1 genes as well as micro-RNA miR-19, miR-96, and miR-206 was studied in control and ERN1 knockdown U87 glioma cells under hypoxia by quantitative polymerase chain reaction.Results. It was shown that the expression level of EDN1, EDNRA, EDNRB, and ECE1 genes was up-regulated in ERN1 knockdown glioma cells in comparison with the control glioma cells, being more significant for endothelin-1. We also observed down-regulation of microRNA miR-206, miR-96, and miR-19a, which have specific binding sites in mRNA EDN1, EDNRA, and EDNRB, correspondingly, and can participate in posttranscriptional regulation of these mRNA expressions. Furthermore, inhibition of ERN1 endoribonuclease lead to up-regulation of EDNRA and ECE1 gene expressions and down-regulation of the expression level of EDN1 and EDNRB genes in glioma cells. Thus, the expression of EDNRA and ECE1 genes is regulated by ERN1 endoribonuclease, but EDN1 and EDNRB genes preferentially by ERN1 protein kinase. We have also shown that hypoxia enhanced the expression of EDN1, EDNRA, and ECE1 genes and that knockdown of ERN1 signaling enzyme function significantly modified the response of all studied gene expressions to hypoxia. Thus, effect of hypoxia on the expression level of EDN1 and ECE1 genes was significantly or completely reduced in ERN1 knockdown glioma cells since the expression of EDNRA gene was down-regulated under hypoxia. Moreover, hypoxia is induced the expression of EDNRB gene in ERN1 knockdown glioma cells.Conclusions. Results of this investigation demonstrate that ERN1 knockdown significantly increased the expression of endothelin-1 and its receptors as well as ECE1 genes by different mechanisms and that all studied gene expressions were sensitive to hypoxia. It is possible that hypoxic regulation of the expression of these genes is a result of complex interaction of variable ERN1 related transcription and regulatory factors with HIF1A and possibly contributed to the control of glioma growth.

show abstract

Section: Discussionsupporting

confidence: 89%

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Minchenko

Tsymbal

Riabovol

et al. 2019

Endocrine Regulations

View full text Add to dashboard Cite

show abstract

“…Kidney function (data presented in the Electronic Supplementary Material (ESM) Table S1 ) was determined in parallel in both control and diabetic animals ( n = 4/group) as previously described [ 16 ]. In brief, anaesthesia was induced using thiobutabarbital and body temperature maintained at 37.5 °C using a servo-controlled heating pad.…”

Section: Methodsmentioning

confidence: 99%

Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging

et al. 2019

Self Cite

View full text Add to dashboard Cite

Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2 weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00216-019-01721-5) contains supplementary material, which is available to authorized users.

show abstract

“…Indeed, ET B receptor-null mice retain water and Na ϩ , likely because of the abolition of effects of ET on aldosterone-sensitive collecting duct cells (16). Also, recent experimental data suggest that ET B receptor signaling in the diabetic kidney improves intrarenal tissue oxygenation (15). Hence, the most likely successful drug candidate would be a highly selective antagonist of ET A receptors (21).…”

Section: Introductionmentioning

confidence: 99%

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ET_A receptor

Dolinina

Rippe

Öberg

2019

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Emerging evidence indicates that endogenous production of endothelin (ET)-1, a 21-amino acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are, however, currently not known. Here, we used size-exclusion chromatography to measure glomerular sieving coefficients for neutral FITC-Ficoll (molecular Stokes-Einstein radius: 15–80 Å, molecular weight: 70 kDa/400 kDa) in anesthetized male Sprague-Dawley rats ( n = 12) at baseline and at 5, 15, 30, and 60 min after intravenous administration of ET-1. In separate experiments, ET-1 was given together with the selective ET type A (ETA) or ET type B (ETB) receptor antagonists JKC-301 and BQ-788, respectively. At both 15 and 30 min postadministration, the glomerular sieving coefficient for macromolecular Ficoll (70 Å) was significantly increased to 4.4 × 10−5 ± 0.7 × 10−5 ( P = 0.024) and 4.5 × 10−5 ± 0.8 × 10−5 ( P = 0.007), respectively, compared with baseline (2.2 × 10−5 ± 0.4 ×10−5). Decreased urine production after ET-1 prevented the use of higher doses of ET-1. Data analysis using the two-pore model indicated changes in large-pore permeability after ET-1, with no changes in the small-pore pathway. Administration of ETA blocker abrogated the permeability changes induced by ET-1 at 30 min, whereas blockade of ETB receptors was ineffective. Mean arterial pressure was only significantly increased at 60 min, being 123 ± 4 mmHg compared with 111 ± 2 mmHg at baseline ( P = 0.02). We conclude that ET-1 evoked small, delayed, and sustained increases in glomerular permeability, mediated via the ETA receptor.

show abstract

Intrarenal activation of endothelin type B receptors improves kidney oxygenation in type 1 diabetic rats

Cited by 6 publications

References 31 publications

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ET_A receptor

Contact Info

Product

Resources

About

Intrarenal activation of endothelin type B receptors improves kidney oxygenation in type 1 diabetic rats

Cited by 6 publications

References 31 publications

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells

Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETA receptor

Contact Info

Product

Resources

About

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ET_A receptor