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Possible mechanisms responsible for mineralocorticoid-induced renal injury

Research Project

Project/Area Number 23590303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKagawa University

Principal Investigator

NISHIYAMA Akira  香川大学, 医学部, 教授 (10325334)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルドステロン / ミネラロコルチコイド受容体 / 腎障害 / 老化 / 腎臓 / レニンアンジオテンシンアルドステロン系
Research Abstract

There is increasing evidence implicating aldosterone, in addition to angiotensin II, in the pathogenesis of hypertension and renal diseases. We have demonstrated that aldosterone causes renal injury through the activation of MR in aldosterone-infused rats, Dahl salt-sensitive hypertensive rats, but in angiotensin II-infused hypertensive mice. In the kidney, MR is expressed not only in destal tubules, but also in glomerular mesangial cells, podocytes, proximal tubular cells, and fibroblasts. In these cells, MR activation causes cell injury via oxidative stress and senescence. These data suggest that MR blockers provide a potential therapeutic approach for patients with hypertension and renal impairment.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (14 results) (of which Invited: 1 results) Remarks (5 results)

  • [Journal Article] High sodium augments angiotensin II-induced vascular smooth muscle cell proliferation through the ERK 1/2-dependent pathway.2014

    • Author(s)
      Liu G, Hitomi H, Rahman A, Nakano D, Mori H, Masaki T, Ma H, Iwamoto T, Kobori H, Nishiyama A.
    • Journal Title

      Hypertens Res.

      Volume: 37(1) Issue: 1 Pages: 13-8

    • DOI

      10.1038/hr.2013.108

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone aggravates glucose intolerance induced by high fructose2013

    • Author(s)
      Sherajee SJ, Rafiq K, Nakano D, Mori H, Kobara H, Hitomi H, Fujisawa Y, Kobori H, Masaki T, Nishiyama A
    • Journal Title

      Eur J Pharmacol

      Volume: 720 Pages: 63-68

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone aggravates glucose intolerance induced by high fructose.2013

    • Author(s)
      Sherajee SJ, Rafiq K, Nakano D, Mori H, Kobara H, Hitomi H, Fujisawa Y, Kobori H, Masaki T, Nishiyama A.
    • Journal Title

      Eur J Pharmacol.

      Volume: 720(1-3) Issue: 1-3 Pages: 63-8

    • DOI

      10.1016/j.ejphar.2013.10.051

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma.2013

    • Author(s)
      Nitta E, Hirooka K, Tenkumo K, Fujita T, Nishiyama A, Nakamura T, Itano T, Shiraga F.
    • Journal Title

      Cell Death Dis.

      Volume: 4 Issue: 7 Pages: e711-e711

    • DOI

      10.1038/cddis.2013.240

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.2013

    • Author(s)
      Rafiq K, Sherajee SJ, Hitomi H, Nakano D, Kobori H, Ohmori K, Mori H, Kobara H, Masaki T, Kohno M, Nishiyama A.
    • Journal Title

      PLoS One.

      Volume: 8(12) Issue: 12 Pages: e82082-e82082

    • DOI

      10.1371/journal.pone.0082082

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of Na⁺/H⁺ exchanger type 1 and intracellular pH in angiotensin II-induced reactive oxygen species generation and podocyte apoptosis.2013

    • Author(s)
      Liu Y, Hitomi H, Diah S, Deguchi K, Mori H, Masaki T, Nakano D, Kobori H, Nishiyama A.
    • Journal Title

      J Pharmacol Sci.

      Volume: 122(3) Pages: 176-83

    • NAID

      10031185411

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin-converting enzyme inhibitor does not suppress renal angiotensin II levels in angiotensin I-infused rats.2013

    • Author(s)
      Ohnishi K, Murase M, Nakano D, Pelisch N, Hitomi H, Kobori H, Morimoto S, Mori H, Masaki T, Ohmori K, Kohno M, Ichihara A, Nishiyama A.
    • Journal Title

      J Pharmacol Sci.

      Volume: 122(2) Pages: 103-8

    • NAID

      10031185402

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone induces insulin-like growth factor-1 receptor and hybrid receptor2012

    • Author(s)
      Sherajee SJ, Fujita Y, Rafiq K, Nakano D, Mori H, Masaki T, Hara T, Kohno M, Nishiyama A, Hitomi H
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Pages: 257-263

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats2012

    • Author(s)
      Kitada K, Nakano D, Liu Y, Fujisawa Y, Hitomi H, Shibayama Y, Shibata H, Nagai Y, Mori H, Masaki T, Kobori H, Nishiyama A
    • Journal Title

      PLoS ONE

      Volume: 7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone induces p21-regulated apoptosis via increased synthesis and secretion of tumour necrosis factor-αin human proximal tubular cells2012

    • Author(s)
      Kitada K, Nakano D, Hitomi H, Kobori H, Deguchi K, Mori H, Masaki T, Nishiyama A
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 39 Pages: 858-863

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone does not contribute to renal p21 expression during the development of angiotensin II-induced hypertension in mice2012

    • Author(s)
      Nakano D, Lei B, Kitada K, Hitomi H, Kobori H, Mori H, Deguchi K, Masaki T, Minamino T, Nishiyama A
    • Journal Title

      Am J Hypertens

      Volume: 25 Pages: 354-358

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone induces p21-regulated apoptosis via increased synthesis and secretion of tumour necrosis factor-α in human proximal tubular cells.2012

    • Author(s)
      Kitada K, Nakano D, Hitomi H, Kobori H, Deguchi K, Mori H, Masaki T, Nishiyama A.
    • Journal Title

      Clin Exp Pharmacol Physiol.

      Volume: 39(10) Issue: 10 Pages: 858-863

    • DOI

      10.1111/j.1440-1681.2012.12001.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oxidative stress-induced glomerular mineralocorticoid receptor activation olimits the benefit of salt reduction in Dahl salt-sensitive rats2012

    • Author(s)
      K.Kitada, H.Shibata, et al.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 7 Pages: e41896-e41896

    • DOI

      10.1371/journal.pone.0041896

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aldosterone Does Not Contribute to Renal p21 Expression During the Development of Angiotensin II-Induced Hypertension in Mice2012

    • Author(s)
      Nakano D, Minamino T, et al
    • Journal Title

      Am J Hypertens

      Volume: 25 Issue: 3 Pages: 354-358

    • DOI

      10.1038/ajh.2011.224

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 2型糖尿病マウスにおけるCCBの降圧を介さないARBの脳腎保護効果の増強2013

    • Author(s)
      西山成, 中野大介, 人見浩史, 小堀浩幸, Rafiq K
    • Organizer
      第86回日本内分泌学会
    • Place of Presentation
      仙台
    • Year and Date
      2013-04-26
    • Related Report
      2013 Final Research Report
  • [Presentation] RAASと腎障害2013

    • Author(s)
      西山成, 小堀浩幸
    • Organizer
      第86回日本内分泌学会
    • Place of Presentation
      仙台
    • Year and Date
      2013-04-26
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 2型糖尿病マウスにおけるCCBの降圧を介さないARBの脳腎保護効果の増強2013

    • Author(s)
      西山 成、中野大介、人見浩史、小堀浩幸、Rafiq K
    • Organizer
      第86回日本内分泌学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] N型カルシウムチャネルを介したアンジオテンシンIIによるポドサイト内カルシウムイオン変動の解析2013

    • Author(s)
      中野大介、Liu Y、人見浩史、小堀浩幸、西山 成
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ダール食塩感受性高血圧ラットで生じる腎組織障害は、減塩とARB・カルシウムチャネル拮抗薬併用による積極的な降圧で減退する2013

    • Author(s)
      西山 成、ラフィーカジ、森川 貴、柴田幹子、岸田真嗣、濱田真宏、北林千津子、小西啓夫、今西政仁
    • Organizer
      第49 回高血圧関連疾患モデル学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腎障害におけるレニン・アンジオテンシン・アルドステロン系の関与2013

    • Author(s)
      西山 成
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 腎内局所レニン・アンジオテンシン・アルドステロン系の病態への関与2012

    • Author(s)
      西山成
    • Organizer
      第55回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-02
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 食塩感受性高血圧で減塩治療しても蛋白尿が改善しないのは, 腎糸球体で生じる酸化ストレスが鉱質コルチコイド受容体を活性化するのが原因である(ラットによる検討)2012

    • Author(s)
      西山成, 中野大介, Liu Y, 藤澤良秀, 人見浩史, 小堀浩幸, 北田研人
    • Organizer
      第1回臨床高血圧フォーラム
    • Place of Presentation
      大阪
    • Year and Date
      2012-05-13
    • Related Report
      2013 Final Research Report
  • [Presentation] アルドステロンにより老化した細胞はTNF-α発現および分泌の増大を介して近位尿細管細胞のアポトーシスを惹起する2012

    • Author(s)
      北田研人, 中野大介, 人見浩史, 小堀浩幸, 西山成
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2012-04-13
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 酸化ストレスは食塩感受性高血圧ラットの腎糸球体における鉱質コルチコイド受容体を活性化し、減塩により得られる蛋白尿抑制効果を減弱する2012

    • Author(s)
      北田研人、中野大介、Liu Y、藤澤良秀、人見浩史、小堀浩幸、西山 成
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 食塩感受性高血圧で減塩治療しても蛋白尿が改善しないのは、腎糸球体で生じる酸化ストレスが鉱質コルチコイド受容体を活性化するのが原因である(ラットによる検討)2012

    • Author(s)
      西山 成、中野大介、LiuY、藤澤良秀、人見浩史、小堀浩幸、北田研人
    • Organizer
      第1回臨床高血圧フォーラム
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] アルドステロンにより老化した細胞はTNF-α分泌を介して近位尿細管細胞のアポトーシスを惹起する2012

    • Author(s)
      北田研人、中野大介、谷田部淳一、人見浩史、小堀浩幸、西山 成
    • Organizer
      第55回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] アンジオテンシンIIは内因性アルドステロン分泌の増加とは関係なく, 腎におけるP21発現を亢進する2011

    • Author(s)
      中野大介, Bai L, Fan Y, 北田研人, 人見浩史, 西山成
    • Organizer
      第34回日本高血圧学会
    • Place of Presentation
      宇都宮
    • Year and Date
      2011-10-21
    • Related Report
      2013 Final Research Report
  • [Presentation] アンジオテンシンIIは内因性アルドステロン分泌の増加とは関係なく、腎におけるP21発現を亢進する

    • Author(s)
      中野大介、Bai L、Fan Y、北田研人、人見浩史、西山 成
    • Organizer
      第34回日本高血圧学会
    • Place of Presentation
      宇都宮
    • Related Report
      2011 Research-status Report
  • [Remarks] ホームページ

    • URL

      http://www.kms.ac.jp/~yakuri/

    • Related Report
      2013 Final Research Report
  • [Remarks] 香川大学医学部薬理学・論文業績

    • URL

      http://www.kms.ac.jp/~yakuri/paper.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 香川大学医学部薬理学・学会業績

    • URL

      http://www.kms.ac.jp/~yakuri/society.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 香川大学医学部薬理学ホームページ

    • URL

      http://www.kms.ac.jp/~yakuri/

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.kms.ac.jp/~yakuri/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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