• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.45-53
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• 1997

In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and $AT_1$ subtypes ($AT_{1A}$ and $AT_{1B}$) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and $AT_{1A}$ mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. $AT_1$B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1371-1377
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• 2006

Gene polymorphisms that are associated with sodium homeostasis in the body, such as $\alpha-adducin$ (ADDI, Gly460Trp), angiotensinogen (AGT, Met235Thr), and angiotensin converting enzyme (ACE, Ins/Del) may increase the risk for the development of hypertension. The purpose of this study was to elucidate the relationship between the singular and combined effects of ADD1, AGT, ACE genotypes, and blood pressure in elderly population. Moreover, we examined the interaction of sodium intake and polymorphisms of aforementioned genes and their effects on blood pressure. Among one hundred and nine female subjects, aged 60 and over (mean 75.9 yr), the major alleles for ADD1, AGT, and ACE polymorphisms in the studied population were Gly (66.1%), Thr (64.2%), Ins (83.5%), respectively. Analysis on the combined effects of genetic variation showed that subjects who were both ADD1 Trp/Trp and ACE Del/Del homozygotes had significantly higher systolic blood pressure (p=0.01). Similarly, ACE Del/Del homozygotes who had AGT Met allele had significantly higher diastolic blood pressure (p<0.001). However, in single-gene analyses, no association was found between any specific genotype and blood pressure. In subjects with low sodium intake, ADD1 Trp/Trp homozygotes had significantly higher systolic blood pressure than subjects who had ADD1 Gly allele (138 mmHg vs. 127 mmHg, p=0.03). There was no difference in blood pressure between ADD1 Trp/Trp and ADD1 Gly/Gly or Gly/Trp, in subjects with high sodium intake. In summary, this study shows that interactions between the ADD1, AGT and ACE genes influence systolic and diastolic blood pressure in elderly subjects, and dietary sodium intake can modulate the effects of ADD1 Gly460Trp polymorphisms on systolic blood pres sure.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.319-328
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• 2020

High fructose intake induces hyperglycemia and hypertension. However, the mechanism by which fructose induces metabolic syndrome is largely unknown. We hypothesized that high fructose intake induces activation of the renin-angiotensin system (RAS), resulting in hypertension and metabolic syndrome. We provided 11-week-old Sprague-Dawley rats with drinking water, with or without 20% fructose, for two weeks. We measured serum renin, angiotensin II (Ang II), and aldosterone (Aldo) using ELISA kits. The expression of RAS genes was determined by quantitative reverse transcription polymerase chain reaction. High fructose intake increased body weight and water retention, regardless of food intake or urine volume. After two weeks, fructose intake induced glucose intolerance and hypertension. High fructose intake increased serum renin, Ang II, triglyceride, and cholesterol levels, but not Aldo levels. High fructose intake increased the expression of angiotensinogen in the liver; angiotensin-converting enzyme in the lungs; and renin, angiotensin II type 1a receptor (AT1aR), and angiotensin II type 1b receptor (AT1bR) in the kidneys. However, expression of AT1aR and AT1bR in the adrenal glands did not increase in rats given fructose. Taken together, these results indicate that high fructose intake induces activation of RAS, resulting in hypertension and metabolic syndrome.

• Journal of Community Nutrition
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• v.8 no.2
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• pp.69-75
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• 2006

Adipose tissue has now been recognized as a rich source of metabolically active molecules that include leptin and angiotensinogen (AGT), the precursor of angiotensin II (Ang II). Both of which have been implicated in the pathogenesis of metabolic alteration and hypertension associated with obesity. In this study, we examined the relationship between body mass index (BMI), adipocyte size, leptin, Ang II secretion and mRNA expression in human adipose tissue obtained from female subjects. Leptin and Ang II were analyzed using specific radioimmunoassay kits following a 48hour tissue culture. Leptin and Ang II secretion varied from 1.4 - 72.1ng/g and 0.8 - 57.3pg/g of tissue respectively. These large individual variations limit significant correlation between BMI, leptin and Ang II secretion. Ang II secretion was significantly higher in the obese than the non-obese (p < 0.05) and positively correlated with BMI. However, no difference in leptin secretion between the obese and the non-obese was observed and leptin secretion showed negative correlation with BMI. No difference in leptin and AGT mRNA expression in adipose tissue between the obese and the non-obese was observed. Although several limitations of this study, we found increased Ang II secretion in obese patients compared with non-obese patients, and positive correlation between AGT and BMI. Observed difference in AGT expression between the obese and the non-obese in this study might be of importance in relation with obesity related hypertension. (J Community Nutrition 8(2): 69-75, 2006)

• YAKHAK HOEJI
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• v.55 no.3
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• pp.203-212
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• 2011

Adipocytes have been known to secrete a number of important proteins called adipokines with roles in energy metabolism, reproduction, cardiovascular function and immunity. In this study we have attempted to identify intensively secretory proteins from 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated into mature adipocytes and then the cells were left in serum-free medium. The supernatant was filtrated and dialyzed. Lyophilized secretome was fractionated by two different methods, 1-D SDS PAGE and RP-FPLC. The tryptic peptides from the gel slices and the FPLC fractions were analyzed by nanoLC/ESI-MS/MS. We identified a total of 303 identical proteins from two methods, 251 proteins from 1-D gel and 184 proteins from RP-FPLC. 86 of them were listed as a secretory protein Finally, we identified many known or unknown secreted proteins existed in the low level including adiponectin, angiotensinogen, bone morphogenetic protein-1 (BMP-1), macrophage migration inhibitory factor (MIF), insulin like growth factor-II (IGF-II), interleukin-6 (IL-6), follistatin-related protein-1, minecan, and resistin. The existence of some of secreted proteins has been confirmed in RNA level. This proteomic experiment is useful for the intensive screening of secretory proteins in many kinds of other cells.

• Childhood Kidney Diseases
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• v.24 no.1
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• pp.1-13
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• 2020

Immunoglobulin (Ig)A vasculitis nephritis (IgAVN), also referred to as Henoch-Schönlein purpura nephritis, is a relatively benign disease in children. However, two 24-year European cohort studies have reported high sustained rates of hypertension, severe proteinuria, and renal dysfunction in patients with IgAVN. Notably, the incidence and exacerbation rates of proteinuria, hypertension, and renal dysfunction during pregnancy were high even in women who recovered from IgAVN before pregnancy. Patients with IgAVN need lifelong care. Trials have been performed to investigate early biomarkers and genes associated with poor prognosis to identify high-risk patients in whom IgAVN may progress to severe renal disease. Urinary IgA/cr, IgM/cr levels, and HLAB35 and angiotensinogen gene expression were shown to be predictors of progression of IgAVN to severe renal dysfunction. The 2019 Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative group published guidelines for pediatric IgAVN, following the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines established in 2012. Compared with the KDIGO guidelines, the SHARE guidelines recommend earlier corticosteroid administration in cases of mild proteinuria (>0.5 g/d). Clinical trials of targeted budesonide delivery to the distal ileum, monoclonal antibody targeting C5, eculizumab and anti-CD20 monoclonal antibody administration, among others are currently underway in patients with IgA nephropathy. It is expected that newer therapeutic agents would become available for IgAVN in the near future. This review summarizes IgAVN with emphasis on recently published literature, including possible preventive strategies, predictive biomarkers for progression of IgAVN, and various treatments.

• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.12-21
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• 2002

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with hypertension in various ethnic groups, but no relation between these polymorphisms and hypertension has yet been systematically evaluated. To assess the relationship between allelic variation of RAS genes and hypertension, we performed the case-control studies using genetic markers in Korean normotensives and hypertensives. The allele and genotype frequencies of RAS genes in Korean population were not significantly different between normotensives and hypertensives. To investigate the distribution of allele frequencies among various populations, the data obtained in this study were compared to those in other ethnic groups studied previously. Except for T174M polymorphism of angiotensinogen (AGT) gene, allele frequencies of RAS genes were different among racial groups. The reason for these differences may be due to the difference in various genetic or environmental background or due to the effects by various sample size studied. In addition, it can be emphasized that carefully designed studies are required to minimize the ethnic heterogeneity of the case and control populations.

• Journal of Preventive Medicine and Public Health
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• v.39 no.2
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• pp.177-183
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• 2006

Objectives : In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T47C, T1641), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. Methods : The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. Results : In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p=0.0403), AGT (M235T) (p=0.0002), and REN (G2646A) (p=0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. Conclusions : This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.52-59
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• 2003

Purpose : The renin-angiotensin system(RAS) plays an important role in renal growth and development. We have studied the prevalence of renal anomalies and documented the association between karyotype and renal anomalies using IVP and ultrasonography. Furthermore, to investigate the impact of RAS gene polymorphism on renal anomaly in Turner syndrome, we examined the ACE I/D genotype, angiotensinogen(AGT) gene M235T, angiotensin receptor type 1(ATR) gene A1166C. Methods : Cytogenetic analysis was performed in 33 Turner syndrome patients on peripheral blood lymphocytes. Ultrasonography(US) of the kidneys and collecting system and intravenous pyelography(IVP) were perfomed in all patients. Nuclear scintigraphy{Tc 99m dimercaptosuccinic acid(DMSA) scan} was also performed for the definite renal diagnosis if indicated. And, ACE I/D genotype, angiotensinogen(AGT) gene M235T, angiotensin receptor type 1(ATR) gene A1166C were examined by PCR amplification of genomic DNA samples. Results : The prevalence of renal anolmalies in Turner syndrome was 36.4%(12/33). The Karyotype 45, X was observed in 18 of the 33 girls(54.5%), of whom 8(44.4%) had renal anomalies. Mosaic karyotypes were observed in 11(33.3%) and four(12.2%) had a non-mosaic structural aberration of the X chromosome. In this group 4(25.7%) had renal anomalies. More renal anomalies were associated with the 45, X karyotype than those with mosaic/structural abnormalities of X chromosome, but the difference was not statistically significant(P>0.05). And, there was no significant differences in the RAS gene polymorphism and allele frequencies between renal anomaly group and normal group in Turner syndrome. Conclusion : The prevalence of renal anolmalies in Turner syndrome was 36.4%. There is no significant differences in the RAS gene polymorphism and allele frequencies between the renal anomaly group and the normal group in Turner syndrome.