Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse

2007 ◽  
Vol 292 (1) ◽  
pp. R453-R461 ◽  
Author(s):  
Hayley Dickinson ◽  
David W. Walker ◽  
E. Marelyn Wintour ◽  
Karen Moritz
Keyword(s):  
Blood Pressure ◽  
Branching Morphogenesis ◽  
Spiny Mouse ◽  
Pcr Analysis ◽  
Nephron Number ◽  
Unbiased Stereology ◽  
Expression Of Genes ◽  
Basal Blood Pressure ◽  
First Time ◽  
Nephron Deficit

We investigated the effects of maternal glucocorticoid exposure in the spiny mouse, a precocial species with a relatively long gestation, few offspring, and in which nephrogenesis is complete before birth. We hypothesized that exposure of the fetus to glucocorticoids before the formation of glomeruli would result in adult hypertensive offspring with fewer nephrons. Furthermore, we hypothesized that this nephron deficit would result from changes in expression of genes involved in branching morphogenesis. Osmotic pumps implanted in pregnant spiny mice at midgestation ( day 20) delivered dexamethasone (dex; 125 μg/kg) or saline for 60 h. Females were killed at day 23 of gestation and kidneys were frozen for real-time PCR analysis or allowed to deliver their offspring. At 20 wk of age, blood pressure was measured in the offspring for 1 wk before nephron number was determined using unbiased stereology. Males and females exposed to dex had significantly fewer nephrons (male: saline: 7,870 ± 27, dex: 6,878 ± 173; female: saline: 7,526 ± 62, dex: 5,886 ± 382; P < 0.001) compared with controls. Dex had no effect on basal blood pressure. Fetal kidneys collected at day 23 of gestation from dex-exposed mothers showed increased mRNA expression of BMP4 ( P < 0.05), TGF-β1 ( P < 0.05), genes known to inhibit branching morphogenesis and gremlin ( P < 0.01), an antagonist of BMP4, compared with saline controls. This study shows for the first time an upregulation of branching morphogenic genes in the fetal kidney in a model of excess maternal glucocorticoids that leads to a nephron deficit in the adult. This study also provides evidence that a reduced nephron number does not necessarily lead to development of hypertension.

The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth

2005 ◽  
Vol 289 (2) ◽  
pp. F273-F279 ◽  
Author(s):  
Hayley Dickinson ◽  
David W. Walker ◽  
Luise Cullen-McEwen ◽  
E. Marelyn Wintour ◽  
Karen Moritz
Keyword(s):  
Kidney Development ◽  
Spiny Mouse ◽  
Nephron Number ◽  
Intrauterine Environment ◽  
Unbiased Stereology ◽  
Spiny Mice ◽  
And Function ◽  
Neonatal Kidney ◽  
Gross Examination ◽  
Nephrogenic Zone

The spiny mouse is relatively mature at birth. We hypothesized that like other organs, the kidney may be more developed in the spiny mouse at birth, than in other rodents. If nephrogenesis is complete before birth, the spiny mouse may provide an excellent model with which to study the effects of an altered intrauterine environment on renal development. Due to its desert adaptation, the spiny mouse may have a reduced cortex-to-medulla ratio but an equivalent total nephron number to the C57/BL mouse. Kidneys were collected from fetal and neonatal spiny mice and sectioned for gross examination of metanephric development. Kidneys were collected from adult spiny mice (10 wk of age), and glomerular number, volume, and cortex-to-medulla ratios were determined using unbiased stereology. Nephrogenesis is complete in spiny mouse kidneys before birth. Metanephrogenesis begins at ∼ day 18, and by day 38 of a 40-day gestation, the nephrogenic zone is no longer present. Spiny mice have a significantly ( P < 0.001) lower total nephron number compared with C57/BL mice, although the total glomerular volume is similar. The cortex-to-medulla ratio of the spiny mouse is significantly ( P < 0.01) smaller. The spiny mouse is the first rodent species shown to complete nephrogenesis before birth. This makes it an attractive candidate for the study of fetal and neonatal kidney development and function. The reduced total nephron number and cortex-to-medulla ratio in the spiny mouse may contribute to its ability to highly concentrate its urine under stressful conditions (i.e., dehydration).

Early glomerular alterations in genetically determined low nephron number

2011 ◽  
Vol 300 (2) ◽  
pp. F521-F530 ◽  
Author(s):  
Kerstin Benz ◽  
Valentina Campean ◽  
Nada Cordasic ◽  
Britta Karpe ◽  
Winfried Neuhuber ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Structural Changes ◽  
Mesangial Cells ◽  
Subsequent Development ◽  
Glomerular Sclerosis ◽  
Pcr Analysis ◽  
Nephron Number ◽  
Peritubular Capillaries

An association between low nephron number and subsequent development of hypertension in later life has been demonstrated. The underlying pathomechanisms are unknown, but glomerular and postglomerular changes have been discussed. We investigated whether such changes are already present in prehypertensive “glial cell line-derived neurotrophic growth factor” heterozygous mice (GDNF+/−) with lower nephron number. Twenty-six-week-old mice [22 GDNF+/−, 29 C57B6 wild-type control (wt)] were used for in vivo experiments with intra-arterial and tail cuff blood pressure measurements. After perfusion fixation, kidneys were investigated with morphological, morphometric, stereological, and immunohistochemical techniques and TaqMan PCR analysis. As expected at this age, blood pressure was comparable between GDNF+/− and wt. Nephron number per kidney was significantly lower in GDNF+/− than in wt (−32.8%, P < 0.005), and mean glomerular volume was significantly higher (+49.5%, P < 0.001). Renal damage scores, glomerular and tubular proliferation, analysis of intrarenal arteries and peritubular capillaries, expression of relevant tubular transporter proteins, as well as gene expression of profibrotic, proinflammatory, or prohypertensive markers were not significantly different between GDNF+/− and wt. Compensatory glomerular hypertrophy in GDNF+/− was accompanied by higher numbers of endothelial and mesangial cells as well as PCNA-positive glomerular cells, whereas podocyte density was significantly reduced. Further electron microscopic analysis showed marked thickening of glomerular basement membrane. In conclusion, lower nephron number is associated with marked early glomerular structural changes, in particular lower capillary supply, reduced podocyte density, and thickened glomerular basement membrane, that may predispose to glomerular sclerosis.

scholarly journals Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jee-Yun Park ◽  
Hee-Young Sohn ◽  
Young Ho Koh ◽  
Chulman Jo
Keyword(s):  
Oxidative Stress ◽  
Crucial Role ◽  
Curcuma Longa ◽  
Expression Plasmid ◽  
Expression Of Genes ◽  
Nrf2 Activation ◽  
First Time ◽  
Nrf2 Protein ◽  
Endogenous Defense ◽  
In Cells

AbstractCurcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.

scholarly journals The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Fluid ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
First Time ◽  
Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

scholarly journals Integrating metabolomics and targeted gene expression to uncover potential biomarkers of fungal/oomycetes-associated disease susceptibility in grapevine

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marisa Maia ◽  
António E. N. Ferreira ◽  
Rui Nascimento ◽  
Filipa Monteiro ◽  
Francisco Traquete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plant Defence ◽  
Breeding Programs ◽  
Analysis Group ◽  
Expression Of Genes ◽  
Leucoanthocyanidin Reductase ◽  
Defence Responses ◽  
Targeted Gene Expression ◽  
Plant Defence Responses ◽  
First Time

Abstract Vitis vinifera, one of the most cultivated fruit crops, is susceptible to several diseases particularly caused by fungus and oomycete pathogens. In contrast, other Vitis species (American, Asian) display different degrees of tolerance/resistance to these pathogens, being widely used in breeding programs to introgress resistance traits in elite V. vinifera cultivars. Secondary metabolites are important players in plant defence responses. Therefore, the characterization of the metabolic profiles associated with disease resistance and susceptibility traits in grapevine is a promising approach to identify trait-related biomarkers. In this work, the leaf metabolic composition of eleven Vitis genotypes was analysed using an untargeted metabolomics approach. A total of 190 putative metabolites were found to discriminate resistant/partial resistant from susceptible genotypes. The biological relevance of discriminative compounds was assessed by pathway analysis. Several compounds were selected as promising biomarkers and the expression of genes coding for enzymes associated with their metabolic pathways was analysed. Reference genes for these grapevine genotypes were established for normalisation of candidate gene expression. The leucoanthocyanidin reductase 2 gene (LAR2) presented a significant increase of expression in susceptible genotypes, in accordance with catechin accumulation in this analysis group. Up to our knowledge this is the first time that metabolic constitutive biomarkers are proposed, opening new insights into plant selection on breeding programs.

Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

1995 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Naoyoshi Minami ◽  
Yutaka Imai ◽  
Jun-Ichiro Hashimoto ◽  
Keishi Abe
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Basal Blood Pressure ◽  
Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

scholarly journals Can Lipoic Acid Attenuate Cardiovascular Disturbances Induced by Ethanol and Disulfiram Administration Separately or Jointly in Rats?

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Bilska-Wilkosz ◽  
Magdalena Kotańska ◽  
Magdalena Górny ◽  
Barbara Filipek ◽  
Małgorzata Iciek
Keyword(s):  
Blood Pressure ◽  
Rat Liver ◽  
Lipoic Acid ◽  
Aldh Activity ◽  
Dihydrolipoic Acid ◽  
Treatment Groups ◽  
Intracellular Compartments ◽  
Electrocardiogram Ecg ◽  
First Time ◽  
All Treatment

The exogenous lipoic acid (LA) is successfully used as a drug in the treatment of many diseases. It is assumed that after administration, LA is transported to the intracellular compartments and reduced to dihydrolipoic acid (DHLA) which is catalyzed by NAD(P)H-dependent enzymes. The purpose of this study was to investigate whether LA can attenuate cardiovascular disturbances induced by ethanol (EtOH) and disulfiram (DSF) administration separately or jointly in rats. For this purpose, we measured systolic and diastolic blood pressure, recorded electrocardiogram (ECG), and estimated mortality of rats. We also studied the activity of aldehyde dehydrogenase (ALDH) in the rat liver. It was shown for the first time that LA partially attenuated the cardiac arrhythmia (extrasystoles and atrioventricular blocks) induced by EtOH and reduced the EtOH-induced mortality of animals, which suggests that LA may have a potential for use in cardiac disturbance in conditions of acute EtOH intoxication. The administration of EtOH, LA, and DSF separately or jointly affected the ALDH activity in the rat liver since a significant decrease in the activity of the enzyme was observed in all treatment groups. The results indicating that LA is an inhibitor of ALDH activity are very surprising.

Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockade

2006 ◽  
Vol 290 (6) ◽  
pp. H2554-H2559 ◽  
Author(s):  
Ryan M. Fryer ◽  
Pamela A. Rakestraw ◽  
Patricia N. Banfor ◽  
Bryan F. Cox ◽  
Terry J. Opgenorth ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Type B ◽  
Selective Antagonist ◽  
Relevant Role ◽  
Basal Blood Pressure ◽  
Baseline Values

The net contribution of endothelin type A (ETA) and type B (ETB) receptors in blood pressure regulation in humans and experimental animals, including the conscious mouse, remains undefined. Thus we assessed the role of ETA and ETB receptors in the control of basal blood pressure and also the role of ETA receptors in maintaining the hypertensive effects of systemic ETB blockade in telemetry-instrumented mice. Mean arterial pressure (MAP) and heart rate were recorded continuously from the carotid artery and daily (24 h) values determined. At baseline, MAP ranged from 99 ± 1 to 101 ± 1 mmHg and heart rate ranged between 547 ± 15 and 567 ± 19 beats/min ( n = 6). Daily oral administration of the ETB selective antagonist A-192621 [10 mg/kg twice daily] increased MAP to 108 ± 1 and 112 ± 2 mmHg on days 1 and 5, respectively. Subsequent coadministration of the ETA selective antagonist atrasentan (5 mg/kg twice daily) in conjunction with A-192621 (10 mg/kg twice daily) decreased MAP to baseline values on day 6 (99 ± 2 mmHg) and to below baseline on day 8 (89 ± 3 mmHg). In a separate group of mice ( n = 6) in which the treatment was reversed, systemic blockade of ETB receptors produced no hypertension in animals pretreated with atrasentan, underscoring the importance of ETA receptors to maintain the hypertension produced by ETB blockade. In a third group of mice ( n = 10), ETA blockade alone (atrasentan; 5 mg/kg twice daily) produced an immediate and sustained decrease in MAP to values below baseline (baseline values = 101 ± 2 to 103 ± 2 mmHg; atrasentan decreased pressure to 95 ± 2 mmHg). Thus these data suggest that ETA and ETB receptors play a physiologically relevant role in the regulation of basal blood pressure in normal, conscious mice. Furthermore, systemic ETB receptor blockade produces sustained hypertension in conscious telemetry-instrumented mice that is absent in mice pretreated with an ETA antagonist, suggesting that ETA receptors maintain the hypertension produced by ETB blockade.

scholarly journals Comparison of Effects on Gene Expression Activity of Low-Molecular-Weight Lychee Fruit Polyphenol (Oligonol®), Adenosine, and Minoxidil in Human Dermal Papilla Cells

2017 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Koji Wakame ◽  
Akifumi Nakata ◽  
Keisuke Sato ◽  
Yoshihiro Mihara ◽  
Jun Takanari ◽  
...  
Keyword(s):  
Cell Lines ◽  
Dna Microarrays ◽  
Food Product ◽  
Dermal Papilla ◽  
Pcr Analysis ◽  
Low Molecular Weight ◽  
Dermal Papilla Cells ◽  
Dermal Papilla Cell ◽  
Expression Of Genes ◽  
Expression Activity

Background: Oligonol® (OLG) is a functional food product and ingredient for cosmetics derived from a lychee fruit polyphenol. It has been reported to act on the skin as an anti-inflammatory and prevent UVB-induced skin damage.Aim: In this study, with the aim of exploring new functionalities of OLG on the scalp, we investigated the effect of OLG on human dermal papilla cells by comparing with adenosine and minoxidil at the genetic level.Method: OLG, adenosine, and minoxidil were applied to human dermal papilla cell lines for 24 h, after which VEGF, FGF-7, WNT5a, and WNT10a mRNA expressions were measured by real-time PCR analysis. Additionally, using DNA microarrays, we investigated the effect on 205 inflammation-related genes.Result: Consequently, in human dermal papilla cell lines, FGF-7 and WNT10a mRNA expression were observed in 100 µg/mL OLG-supplemented cells. The results of the DNA microarray analysis showed that 10 genes were suppressed by OLG.Conclusions: OLG may be expected to affect function of human dermal papilla cell by regulating the expression of genes related to cell proliferation and inflammation.

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