Takeda, Ayano



Research Centers and Institutes, Health Center (Hiyoshi)


Assistant Professor/Senior Assistant Professor

Academic Background 【 Display / hide

  • 1996.04

    Keio University, 医学部


  • 2004.04

    Keio University, 医学研究科

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

Academic Degrees 【 Display / hide

  • 博士, Keio University, Coursework, 2010.07

    NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor.


Research Keywords 【 Display / hide

  • aldosterone

  • mineralocorticoid receptor


Papers 【 Display / hide

  • Features of and preventive measures against hypertension in the young

    Kawabe H., Azegami T., Takeda A., Kanda T., Saito I., Saruta T., Hirose H.

    Hypertension Research (Hypertension Research)  42 ( 7 ) 935 - 948 2019.07

    ISSN  09169636

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    © 2019, The Author(s). The Japanese hypertension guidelines report that essential hypertension is detected in 1–3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one’s health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.

  • Low birth weight is associated with decline in renal function in Japanese male and female adolescents

    Murai-Takeda A., Kanda T., Azegami T., Hirose H., Inokuchi M., Tokuyama H., Wakino S., Tokumura M., Kawabe H., Mori M., Itoh H.

    Clinical and Experimental Nephrology (Clinical and Experimental Nephrology)   2019

    ISSN  13421751

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    © 2019, Japanese Society of Nephrology. Background: Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated. In this study, we investigated the sex-specific effect of LBW on renal function. Methods: Annual cross-sectional data of 2417 Japanese adolescents (males 1736; females 681), aged 15–16 years, were evaluated over 8 years (2007–2014). Results: Over the study period, mean birth weights decreased significantly in males (p < 0.01) and females (p < 0.05). Furthermore, both sexes showed significant decrease in estimated glomerular filtration rates corresponding to the birth weight reduction. The prevalence of CKD stage 2 also increased in males (from 26.0 to 32.4%, p < 0.01) and females (from 6.3 to 18.5%, p < 0.05). The incidence of CKD stage 2 was significantly related to history of LBW (males: odds ratio 1.73; 95% confidence interval 1.06–2.80; p < 0.05; females: odds ratio 3.29; 95% confidence interval 1.25–8.02; p < 0.05). Conclusions: Our data revealed that renal function and birth weight have decreased over time, in healthy Japanese adolescents. In view of the recent declining trend demonstrated by birth weight in Japan, we speculate that the prevalence of CKD might increase in the future.

  • Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization

    Mitsuishi Y., Shibata H., Kurihara I., Kobayashi S., Yokota K., Murai-Takeda A., Hayashi T., Jo R., Nakamura T., Morisaki M., Itoh H.

    Molecular and Cellular Endocrinology (Molecular and Cellular Endocrinology)  473   89 - 99 2018.09

    ISSN  03037207

     View Summary

    © 2018 Elsevier B.V. Activation of mineralocorticoid receptor (MR) is evoked by aldosterone, and it induces hypertension and cardiovascular disease when it's concomitant with excessive salt loading. We have proposed the notion of “MR-associated hypertension” in which add-on therapy of MR blockers is effective even though serum aldosterone level is within normal range. To elucidate its underlying molecular mechanism, we focused on the effect of epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) activation on MR activity. Epidermal growth factor (EGF) administration increased MR transcriptional activity through EGFR/ERK pathway and increased protein level by counteracting MR ubiquitylation in vitro. EGF administration in vivo also increased MR protein level and target gene expression in kidney, which were decreased by EGFR inhibitor. In addition, the administration of EGFR inhibitor lowered systolic blood pressure and MR activity in DOCA/salt-treated mice. In conclusion, EGFR/ERK pathway activation is considered as one of the underlying mechanisms of aberrant MR activation and EGFR/ERK pathway blockade could be an alternative approach for the prevention of MR-related cardiovascular events.

  • Intestinal mineralocorticoid receptor contributes to epithelial sodium channel–mediated intestinal sodium absorption and blood pressure regulation

    Nakamura T., Kurihara I., Kobayashi S., Yokota K., Murai-Takeda A., Mitsuishi Y., Morisaki M., Kohata N., Oshima Y., Minami Y., Shibata H., Itoh H.

    Journal of the American Heart Association (Journal of the American Heart Association)  7 ( 13 )  2018.07

     View Summary

    © 2018 The Authors. Background-—Mineralocorticoid receptor (MR) has pathological roles in various cell types, including renal tubule cells, myocytes, and smooth muscle cells; however, the role of MR in intestinal epithelial cells (IECs) has not been sufficiently evaluated. The intestine is the sensing organ of ingested sodium; accordingly, intestinal MR is expected to have essential roles in blood pressure (BP) regulation. Methods and Results-—We generated IEC-specific MR knockout (IEC-MR-KO) mice. With a standard diet, fecal sodium excretion was 1.5-fold higher in IEC-MR-KO mice, with markedly decreased colonic expression of b- and c-epithelial sodium channel, than in control mice. Urinary sodium excretion in IEC-MR-KO mice decreased by 30%, maintaining sodium balance; however, a low-salt diet caused significant reductions in body weight and BP in IEC-MR-KO mice, and plasma aldosterone exhibited a compensatory increase. With a high-salt diet, intestinal sodium absorption markedly increased to similar levels in both genotypes, without an elevation in BP. Deoxycorticosterone/salt treatment elevated BP and increased intestinal sodium absorption in both genotypes. Notably, the increase in BP was significantly smaller in IEC-MR-KO mice than in control mice. The addition of the MR antagonist spironolactone to deoxycorticosterone/salt treatment eliminated the differences in BP and intestinal sodium absorption between genotypes. Conclusions-—Intestinal MR regulates intestinal sodium absorption in the colon and contributes to BP regulation. These regulatory effects are associated with variation in epithelial sodium channel expression. These findings suggest that intestinal MR is a new target for studying the molecular mechanism of hypertension and cardiovascular diseases.

  • Temporal trends in renal function and birthweight in Japanese adolescent males (1998-2015)

    Kanda T., Takeda A., Hirose H., Abe T., Urai H., Inokuchi M., Wakino S., Tokumura M., Itoh H., Kawabe H.

    Nephrology Dialysis Transplantation (Nephrology Dialysis Transplantation)  33 ( 2 ) 304 - 310 2018.02

    ISSN  09310509

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    © 2017 The Author . Published by Oxford University Press on behalf of ERA-EDTA. Background Low birthweight (LBW) is a worldwide public health problem, demonstrating an increasing incidence in developed countries, including Japan. LBW is also a risk factor for later development of chronic kidney disease (CKD). To date, studies have not evaluated the population impacts of increasing LBW rates on renal function. Methods Estimated glomerular filtration rate (EGFR) was evaluated in 3737 Japanese adolescent males (15-16 years old) using annual cross-sectional data over an 18-year period (1998-2015). Results Between the initial (1998-2003) and final (2010-15) periods of the study, the mean birthweight decreased from 3213.4 ± 383.8 to 3116.2 ± 382.3 g and the LBW rate increased from 2.5 to 5.5% (both P ≤ 0.01). Additionally, the mean EGFR decreased from 105.1 ± 15.9 to 97.4 ± 13.8 mL/min/1.73 m 2 and the prevalence of mildly reduced renal function (EGFR ≤ 60-<90 mL/min/1.73 m 2) increased from 16.4 to 30.0% (both P ≤ 0.01), most evident in the LBW group (from 10.3 to 41.7%, P ≤0.01). The prevalence of proteinuria also increased significantly. Mildly reduced renal function was significantly associated with LBW [odds ratio (LBW 3000-3999 g) 1.51; 95% confidence interval 1.00-2.55; P = 0.047]. Conclusions In this population of Japanese adolescents, the frequency of mildly reduced renal function increased as the LBW frequency increased. Our findings may have implications for the broader Japanese population as well as for other populations in which the prevalence of LBW is increasing.

Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 増大する副腎嚢胞に対して副腎部分切除術を行った1例

    上妻 嵩英, 栗原 勲, 小林 佐紀子, 横田 健一, 武田 彩乃, 三石 木綿子, 乃村 元子, 高畑 尚, 宮下 和季, 武田 利和, 大家 基嗣, 亀山 香織, 伊藤 裕

    日本内分泌学会雑誌 ((一社)日本内分泌学会)  95 ( 2 ) 742 - 742 2019.10

    ISSN  0029-0661

  • 低出生時体重は男女とも青年期における腎機能低下に関与する

    神田 武志, 武田 彩乃, 畔上 達彦, 徳山 博文, 脇野 修, 伊藤 裕

    日本腎臓学会誌 ((一社)日本腎臓学会)  61 ( 3 ) 316 - 316 2019.05

    ISSN  0385-2385

  • 原発性アルドステロン症の副腎部分切除術選択における区域別副腎静脈サンプリングの有用性

    乃村 元子, 栗原 勲, 小林 佐紀子, 横田 健一, 宮下 和季, 武田 彩乃, 三石 木綿子, 高畑 尚, 南 悠季子, 齋藤 洸平, 上妻 嵩英, 中塚 誠之, 武田 利和, 伊藤 裕

    日本高血圧学会臨床高血圧フォーラムプログラム・抄録集 ((NPO)日本高血圧学会)  8回   171 - 171 2019.05

  • 超高齢で副腎摘除術を行った褐色細胞腫の2例

    上妻 嵩英, 栗原 勲, 小林 佐紀子, 横田 健一, 宮下 和季, 武田 彩乃, 永久 太一, 菊地 理恵子, 武田 利和, 大家 基嗣, 亀山 香織, 伊藤 裕

    日本内分泌学会雑誌 ((一社)日本内分泌学会)  95 ( 1 ) 483 - 483 2019.04

    ISSN  0029-0661

  • シンチグラフィー陰性を呈したサブクリニカルクッシング症候群の一例

    菊地 理恵子, 栗原 勲, 横田 健一, 宮下 和季, 小林 佐紀子, 武田 彩乃, 上妻 嵩英, 武田 利和, 大家 基嗣, 亀山 香織, 伊藤 裕

    日本内分泌学会雑誌 ((一社)日本内分泌学会)  95 ( 1 ) 468 - 468 2019.04

    ISSN  0029-0661

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • アルドステロン過剰に伴う高血圧性臓器障害における性差の検討


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 武田 彩乃, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • The role of glycosylation of renal mineralocorticoid receptor in hypertension and renal dysfunction.


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 武田 彩乃, Grant-in-Aid for Young Scientists (B), Principal Investigator

     View Summary

    We established podocyte-specific and renal tubule-secific O-GlcNAc transferase (OGT) transgenic mouse models and analyzed their phenotypes to elucidate the effect of glycosylation of mineralocorticoid receptor (MR) in hypertension and renal dysfunction.
    MR activity examined in kidney tissues was enhanced in renal tubule-specific OGT transgenic mice, which suggested that the glycosylation of MR could be involved in the underlying mechanism of “MR-associated hypertension” in diabetes.


Courses Taught 【 Display / hide