The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion

2013 ◽  
Vol 304 (5) ◽  
pp. F578-F584 ◽  
Author(s):  
Katharina Machura ◽  
Elina Iankilevitch ◽  
Björn Neubauer ◽  
Franz Theuring ◽  
Armin Kurtz
Keyword(s):  
Enzyme Inhibitor ◽  
Plasma Renin ◽  
Mrna Levels ◽  
Wild Type ◽  
Mouse Vas Deferens ◽  
Salt Diet ◽  
Adult Kidney ◽  
Renin Mrna ◽  
And Function

On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life

1992 ◽  
Vol 262 (3) ◽  
pp. R459-R463 ◽  
Author(s):  
W. V. Page ◽  
S. Perlman ◽  
F. G. Smith ◽  
J. L. Segar ◽  
J. E. Robillard
Keyword(s):  
Gene Expression ◽  
Plasma Renin ◽  
Renal Nerves ◽  
Mrna Levels ◽  
Angiotensin I ◽  
Fetal Sheep ◽  
Close Analysis ◽  
Renin Gene ◽  
Renin Mrna

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Control of renin secretion from kidneys with renin cell hyperplasia

2014 ◽  
Vol 306 (3) ◽  
pp. F327-F332 ◽  
Author(s):  
Birgül Kurt ◽  
Christian Karger ◽  
Charlotte Wagner ◽  
Armin Kurtz
Keyword(s):  
Plasma Renin ◽  
Renin Secretion ◽  
Ang Ii ◽  
Loss Of Function ◽  
Wild Type ◽  
Cell Hyperplasia ◽  
Absolute Level ◽  
Relative Level ◽  
Adult Kidney ◽  
Renin Mrna

In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS−/− mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS−/− kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca2+ was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca2+ on renin secretion in the same manner in kidneys of AS−/− mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β1-adrenergic receptors, ANG II type 1 receptors, and connexin40.

Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats

2000 ◽  
Vol 278 (6) ◽  
pp. H2115-H2123 ◽  
Author(s):  
Erik Øie ◽  
Reidar Bjørnerheim ◽  
Ole Petter F. Clausen ◽  
Håvard Attramadal
Keyword(s):  
Cyclosporin A ◽  
Myocardial Hypertrophy ◽  
Plasma Renin ◽  
Mrna Levels ◽  
Tibial Length ◽  
And Function ◽  
Myocardial Gene Expression ◽  
Derivatives Of ◽  
Fractional Shortening

Calcineurin has recently been implicated as a mediator in the signaling pathways that transform intracellular calcium signals to the phenotype of myocardial hypertrophy. The present study was conducted to examine the effects of cyclosporin A (CsA), an inhibitor of calcineurin, on myocardial hypertrophy and remodeling during congestive heart failure (CHF) in rats. After ligation of the left coronary artery, rats were randomized to treatment with CsA or vehicle for 14 days. Compared with vehicle, CsA substantially attenuated myocardial hypertrophy in the CHF rats as assessed by alterations in ventricular weight-to-tibial length ratios ( P < 0.05). Myocardial gene expression of skeletal α-actin was also reduced in the failing left ventricle (LV) after treatment with CsA ( P < 0.05), although the mRNA levels were still substantially elevated relative to those of sham rats. CsA-induced inhibition of compensatory myocardial hypertrophy in the CHF rats led to increased dilatation of the LV cavity and reduced fractional shortening and peak positive and negative first derivatives of LV pressure ( P < 0.05). Plasma renin and endothelin-1 levels were increased in the CHF-CsA rats, providing humoral cues of aggravated cardiac function. Thus this study supports a crucial role of calcineurin-dependent pathways in the mechanisms of compensatory myocardial hypertrophy during CHF. In addition, our data indicate that inhibition of compensatory myocardial hypertrophy exerts detrimental effects on cardiac remodeling and function after myocardial infarction.

scholarly journals Dense-core vesicle proteins IA-2 and IA-2β affect renin synthesis and secretion through the β-adrenergic pathway

2009 ◽  
Vol 296 (2) ◽  
pp. F382-F389 ◽  
Author(s):  
Soo Mi Kim ◽  
Franziska Theilig ◽  
Yan Qin ◽  
Tao Cai ◽  
Diane Mizel ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Salt Intake ◽  
Plasma Renin ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Mrna Levels ◽  
Wild Type ◽  
Dense Core Vesicles ◽  
Renin Synthesis ◽  
Renin Mrna

IA-2 and IA-2β, major autoantigens in type 1 diabetes, are transmembrane proteins in dense-core vesicles, and their expression influences the secretion of hormones and neurotransmitters. The present experiments were performed to examine whether IA-2 and IA-2β modulate the release of renin from dense-core vesicles of juxtaglomerular granular cells in the kidney. Plasma renin concentration (PRC; ng angiotensin I·ml−1·h−1) was significantly reduced in mice with null mutations in IA-2, IA-2β, or both IA-2 and IA-2β compared with wild-type mice (876 ± 113, 962 ± 130, and 596 ± 82 vs. 1,367 ± 93; P < 0.01, P < 0.02, and P < 0.001). Renin mRNA levels were reduced to 26.4 ± 5.1, 39 ± 5.4, and 35.3 ± 5.5% of wild-type in IA-2−/−, IA-2β−/−, and IA-2/IA-2β−/− mice. Plasma aldosterone levels were not significantly different among genotypes. The regulation of PRC by furosemide and salt intake, and of aldosterone by salt intake, was maintained in all genotypes. IA-2 and IA-2β expression did not colocalize with renin but showed overlapping immunoreactivity with tyrosine hydroxylase. While propranolol reduced PRC in wild-type mice, it had no effect on PRC in IA-2/ IA-2β−/− mice. Renal tyrosine hydroxylase mRNA and immunoreactivity were reduced in IA-2/IA-2β−/− mice as was the urinary excretion of catecholamines. We conclude that IA-2 and IA-2β are required to maintain normal levels of renin expression and renin release, most likely by permitting normal rates of catecholamine release from sympathetic nerve terminals.

scholarly journals Temporary Treatment of Prepubescent Rats with Angiotensin Inhibitors Suppresses the Development of Hypertensive Nephrosclerosis

2001 ◽  
Vol 12 (4) ◽  
pp. 659-666
Author(s):  
HIDEAKI NAKAYA ◽  
HIROYUKI SASAMURA ◽  
MATSUHIKO HAYASHI ◽  
TAKAO SARUTA
Keyword(s):  
Renal Disease ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Mrna Levels ◽  
Hypertensive Nephrosclerosis ◽  
Spontaneously Hypertensive ◽  
Renin Mrna ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Hypertensive nephrosclerosis is a leading cause of end-stage renal disease; therefore, strategies to prevent the development of renal disease require close study. Here it is demonstrated that transient treatment of prepubescent rats with angiotensin inhibitors attenuated their susceptibility to the development of hypertensive nephrosclerosis after maturation. Stroke-prone spontaneously hypertensive Izumo strain rats were divided into four groups, treated with vehicle, the angiotensin-converting enzyme inhibitor (ACEI) delapril (40 mg/kg per d), the angiotensin receptor antagonist (AT1R-Ant) candesartan cilexetil (1 mg/kg per d), or the vasodilator hydralazine (25 mg/kg per d) from weaning to puberty (3 to 10 wk of age), and then monitored without treatment for 6 mo. BP in the ACEI- and AT1R-Ant-treated groups remained significantly decreased, compared with the untreated and hydralazine-treated groups. Moreover, marked proteinuria and nephrosclerosis developed in the untreated and hydralazine-treated groups at 30 wk but were suppressed in the ACEI- and AT1R-Ant-treated groups. Of interest, plasma renin activity, plasma angiotensin II concentrations, and renal renin mRNA levels were reduced by >50% in the ACEI- and AT1R-Ant-treated rats, suggesting that the treatments may have attenuated the development of nephrosclerosis by overcoming the susceptibility of stroke-prone spontaneously hypertensive rats to overactivation of the renin-angiotensin system.

Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2541-2553 ◽  
Author(s):  
Johanna Laurikkala ◽  
Johanna Pispa ◽  
Han-Sung Jung ◽  
Pekka Nieminen ◽  
Marja Mikkola ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hair Follicles ◽  
Wild Type ◽  
Mutant Mouse Embryos ◽  
Anhidrotic Ectodermal Dysplasia ◽  
Embryonic Morphogenesis ◽  
Hair Follicle Development ◽  
And Function ◽  
Insight Into

X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for β-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

scholarly journals TLR7 modulating B-cell immune responses in the spleen of C57BL/6 mice infected with Schistosoma japonicum

2021 ◽  
Vol 15 (11) ◽  
pp. e0009943
Author(s):  
Haixia Wei ◽  
Hongyan Xie ◽  
Jiale Qu ◽  
Anqi Xie ◽  
Shihao Xie ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Gene Knockout ◽  
Innate Immune ◽  
Wild Type ◽  
Cell Responses ◽  
Splenic Cells ◽  
And Function ◽  
Egg Antigen

B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S. japonicum for 5–6 weeks. The percentages and numbers of B cells increased in the infected mice (p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S. japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice (p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice (p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S. japonicum infected C57BL/6 mice.

Abstract 196: Role of Collecting Duct Renin in Blood Pressure Regulation

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Nirupama Ramkumar ◽  
Deborah Stuart ◽  
Sara Rees ◽  
Curt Sigmund ◽  
Donald E Kohan
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Dna Recombination ◽  
Plasma Renin ◽  
Blood Pressure Regulation ◽  
P System ◽  
Mrna Levels ◽  
Pressure Regulation ◽  
Renin Mrna ◽  
Exon 1

Recent studies propose that collecting duct (CD) renin is an important modulator of blood pressure regulation, especially in conditions such as angiotensin-II infused hypertension. We used gene targeting to generate a CD-specific renin knockout (KO) to assess if CD derived renin can regulate BP. Utilizing the Cre lox P system, exon 1 of the renin gene was ablated specifically in the CD. BP was recorded via telemetry and plasma and urine were collected in metabolic cages on normal, high and low Na diets. DNA recombination showed kidney specific recombination in KO mice. Compared to floxed mice, CD renin KO mice had 70 % lower medullary renin mRNA levels and 90% lower renin mRNA in micro-dissected cortical and inner medullary CD tubules. Urinary renin levels were significantly lower in the KO mice on normal and low Na diets (45% of floxed levels) but not with high Na intake. Plasma renin concentration was significantly higher in the KO mice on all three diets. While BP was similar between the two groups on all three diets, infusion of Ang-II delayed the increase in BP in the CD renin KO group for at least 4 days post-infusion. These findings suggest that CD renin likely plays a role in normal BP regulation (evidenced by an increase in PRC) and in response to AngII infusion.

The role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in Hirschsprung associated enterocolitis

2020 ◽  
Author(s):  
Feng Chen ◽  
Xiaoyu Wei ◽  
Xiaohua Chen ◽  
Lei Xiang ◽  
Xinyao Meng ◽  
...  
Keyword(s):  
Western Blotting ◽  
Mrna Level ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Wild Type ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Phosphorylated Stat3 ◽  
Morphology Changes

Abstract Background To investigate the role and the underlying mechanism of the α7nAChR-mediated cholinergic anti-inflammatory pathway in the pathogenesis of Hirschsprung(HSCR) associated enterocolitis（HAEC）. Methods Experimental group:twenty-one-day-old Ednrb-/- mice were selected (n=10), with comparable-age wild type(Ednrb+/+) mice controls (n=10). Intestinal samples were collected. The experimental colons were divided into narrow and dilated segments according to morphology changes. The control colons were divided into distal and proximal segments.Colon HE staining was used to judge HAEC.Acetylcholine levels in colon was measured using enzyme-linked immunosorbent assays. Detected phosphorylated Jak2 (p-Jak2), Jak2, phosphorylated Stat3 (p-Stat3), Stat3, phosphorylated IκBα (p-IκBα) and IκBα were studied by Western blotting; mRNA levels of Jak2, Stat3, and IκBα were detected by RT-qPCR. Results Colon HE staining indicated that HAEC mainly occured in the dilated segments of HSCR mice (Ednrb-/- mice) (EDNRB-P).Acetylcholine content in EDNRB-P was significantly lower than that in the narrow segments (EDNRB-D) (P<0.05). Western blotting showed that the Jak2, p-Jak2, Stat3 and p-Stat3 levels in EDNRB-D were significantly higher than those in EDNRB-P (P<0.05). The p-IκBα and IκBα levels in EDNRB-P were significantly higher than those in EDNRB-D(P<0.05). The mRNA levels of Jak2 and Stat3 in EDNRB-D were higher than those in EDNRB-P, but the IκBα mRNA level was significantly lower than that in EDNRB-P (P<0.05). Conclusions During HAEC, the inflammation in the dilated segment was more severe ,while in the narrow segment there was no obvious inflammatory reaction and the content of acetylcholine was higher, which was associated with the α7nAChR-mediated cholinergic anti-inflammatory pathway.

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