Podocyte injury in diabetic nephropathy: a novel approach by modulation of posttranslational modification of mineralocorticoid receptor proteins
Project/Area Number |
18K08214
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Oita University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | アルドステロン / ミネラルコルチコイド受容体 / 慢性腎臓病 / ポドサイト / インドキシル硫酸 / 糖尿病性腎症 / 蛋白修飾 |
Outline of Final Research Achievements |
To elucidate relationship between mineralocorticoid receptor (MR) activation and renal dysfunction in chronic kidney disease (CKD), we utilized in vitro cultured cells and 5/6 nephrectomized CKD rats. In renal fibroblast COS-7 cells, administration of indoxyl sulfate (IS) potentiated MR transactivation as well as increased MR protein levels, whereas co-administration of anti-oxidant, alpha-lipoic acid reversed the MR levels as well as MR transactivation. In CKD rats, both renal MR protein and Sgk-1 mRNA levels were elevated in CKD rats, whereas administration of AST-120, an IS-lowering agent, decreased MR levels and its transactivation. Based on these findings, IS enhances MR transactivation due in part to elevation of MR protein levels in the pathogenesis of CKD.
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Academic Significance and Societal Importance of the Research Achievements |
学術的意義としては、慢性腎臓病でポドサイト障害などが進行する原因として、体内に蓄積する尿毒素のインドキシル硫酸が、血中アルドステロン濃度の上昇がなくてもMR蛋白レベルを増加させることによるMR活性化をきたすことが関与することを初めて明らかにできた。 社会的意義としては、糖尿病性腎症などによる慢性腎臓病から透析導入者が増加が年々続いており、透析導入だけでなく、それまでの過程で心血管疾患による死亡が増えており、大きな社会的問題となっている。その原因の一つを本研究が明らかにできたことで、早期からのMRのブロックが慢性腎臓病患者の予後改善につながることが強く期待される。
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Report
(4 results)
Research Products
(100 results)
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[Journal Article] α-Tocopherol Suppresses Hepatic Steatosis by increasing CPT-1 Expression in a Mouse Model of Diet-induced Non-alcoholic Fatty Liver Disease2021
Author(s)
Tokoro M, Gotoh K, Kudo Y, Hirashita Y, Iwao M, Arakawa M, Endo M, Oribe J, Masaki T, Honda K, Kakuma T, Seike M, Murakami K, Shibata H.
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Volume: 7
Pages: 91-99
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[Journal Article] Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism2021
Author(s)
Satoh F, Ito S, Itoh H, Rakugi H, Shibata H, Ichihara A, Omura M, Takahashi K, Okuda Y, Iijima S
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Journal Title
Hypertension Research
Volume: 4
Pages: 464-472
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[Journal Article] Development of a new chemiluminescent enzyme immunoassay using a two-step sandwich method for measuring aldosterone concentrations2021
Author(s)
Ozeki Y, Tanimura Y, Nagai S, Nomura T, Kinoshita M, Shibuta K, Matsuda N, Miyamoto S, Yoshida Y, Okamoto M, Gotoh K, Masaki T, Kambara K, Shibata H.
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Journal Title
Diagnostics
Volume: 11
Pages: 433-433
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[Journal Article] Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy2020
Author(s)
Fukuda A, Minakawa A, Kikuchi M, Sato Y, Nagatomo M, Nakamura S, Mizoguchi T, Fukunaga N, Shibata H, Naik AS, Wiggins RC, Fujimoto S
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Journal Title
Scientific Reports
Volume: 10
Pages: 18209-18209
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[Journal Article] Sensitive and selective quantification of mid-regional proadrenomedullin in human plasma using ultra-performance liquid chromatography coupled with tandem mass spectrometry.2020
Author(s)
Iwao M, Suzuki Y, Tanaka R, Koyama T, Ozaki E, Nakata T, Aoki K, Fukuda A, Sato Y, Kuriyama N, Fukunaga N, Sato F, Katagiri F, Ohno K, Shibata H, Mimata H, Itoh H.
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Journal Title
J Pharm Biomed Anal.
Volume: 183
Pages: 113168-113168
DOI
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Peer Reviewed / Open Access
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[Journal Article] Historical changes and between-facility differences in adrenal venous sampling for primary aldosteronism in Japan.2020
Author(s)
Fujii Y, Takeda Y, Shibata H(18番目), Kamemura K, Otsuki M, Yamamto K, Ogo A, Yanase T, Okamura S, Miyauchi S, Fujita M, Suzuki T, Umakoshi H, Ogasawara T, Tsuiki M, Naruse M; JPAS Study Group.
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Journal Title
J Hum Hypertens.
Volume: 4
Pages: 34-42
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[Journal Article] Predictors of Clinical Success After Surgery for Primary Aldosteronism in the Japanese Nationwide Cohort.2019
Author(s)
Morisaki M, Kurihara I, Itoh H, Naruse M, Takeda Y, Katabami T, Ichijo T, Wada N, Yoshimoto T, Ogawa Y, Sone M, Tsuiki M, Shibata H, Kawashima J, Fujita M, Watanabe M, Matsuda Y, Kobayashi H, Suzuki T; JPAS Study Group.
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Journal Title
J Endocr Soc.
Volume: 3
Pages: 2012-2022
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[Journal Article] The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).2019
Author(s)
Umemura S, Arima H, Shibata H (35番目), Shimosawa T, Suzuki H, Takahashi S, Tamura K, Tomiyama H, Tsuchihashi T, Ueda S, Uehara Y, Urata H, Hirawa N.
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Journal Title
Hypertens Res
Volume: 42
Pages: 1235-1481
Related Report
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[Journal Article] Clinical and biochemical outcomes after adrenalectomy and medical treatment in patients with unilateral primary aldosteronism.2019
Author(s)
Katabami T, Fukuda H, Shibata H (22番目), Kamemura K, Otsuki M, Fujii Y, Yamamoto K, Ogo A, Yanase T, Suzuki T, Naruse M; JPAS/JRAS Study Group.
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Journal Title
J Hypertens.
Volume: 37
Pages: 1513-1520
Related Report
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[Journal Article] Influence of antihypertensive drugs in the subtype diagnosis of primary aldosteronism by adrenal venous sampling.2019
Author(s)
Nagasawa M, Yamamoto K, Shibata H (25番目), Kamemura K, Otsuki M, Fujii Y, Ogo A, Okamura S, Miyauchi S, Yanase T, Suzuki T, Kawamura T, Naruse M; JPAS Study Group.
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Journal Title
J Hypertens.
Volume: 37
Pages: 1493-1499
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[Journal Article] Relationships between computed tomography-assessed density, abdominal fat volume, and glucose metabolism after sleeve gastrectomy in Japanese patients with obesity.2019
Author(s)
Ozeki Y, Masaki T, Yoshida Y, Okamoto M, Anai M, Gotoh K, Endo Y, Ohta M, Inomata M, Shibata H.
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Journal Title
Endocr J.
Volume: 66
Pages: 605-613
NAID
Related Report
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[Journal Article] High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan.2019
Author(s)
Akehi Y, Yanase T, Shibata H (25番目), Kamemura K, Otsuki M, Fujii Y, Yamamoto K, Ogo A, Okamura S, Miyauchi S, Fukuoka T, Izawa S, Hashimoto S, Yamada M, Yoshikawa Y, Kai T, Suzuki T, Kawamura T, Naruse M; Japan Primary Aldosteronism Study Group.
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Journal Title
Diabetes Care
Volume: 42
Pages: 938-945
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[Journal Article] A synonymous VHL variant in exon 2 confers susceptibility to familial pheochromocytoma and von Hippel-Lindau disease.2019
Author(s)
Flores SK, Cheng Z, Jasper AM, Natori K, Okamoto T, Tanabe A, Gotoh K, Shibata H, Sakurai A, Nakai T, Wang X, Zethoven M, Balachander S, Aita Y, Young W, Zheng S, Takekoshi K, Nakamura E, Tothill RW, Aguiar RCT, Dahia PLM
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Journal Title
J Clin Endocrinol Metab
Volume: in press
Issue: 9
Pages: 3826-3834
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effects of Sleeve Gastrectomy on Blood Pressure and the Renal Renin-Angiotensin System in Rats with Diet-Induced Obesity.2019
Author(s)
Yoshida Y, Gotoh K, Masaki T, Ozeki Y, Tokoro M, Kudo A, Ozaki T, Okamoto M, Chiba S, Watanabe K, Ohta M, Inomata M, Shibata H.
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Journal Title
Obesity
Volume: 27
Pages: 785-792
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[Journal Article] Impact of adrenocorticotropic hormone stimulation during adrenal venous sampling on outcomes of primary aldosteronism.2019
Author(s)
Takeda Y, Umakoshi H, Takeda Y, Yoneda T, Kurihara I, Katabami T, Ichijo T, Wada N, Yoshimoto T, Ogawa Y, Kawashima J, Sone M, Takahashi K, Watanabe M, Matsuda Y, Kobayashi H, Shibata H, Kamemura K, Otsuki M, Fujii Y, Yamamto K, Ogo A, Yanase T, Suzuki T, Naruse M; JPAS Study Group.
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Journal Title
J Hypertens.
Volume: 37
Pages: 1077-1082
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[Journal Article] SGLT2阻害薬(ダパグリフロジン)を服用中にフルニエ壊疽を発症した高齢2型糖尿病の1例2019
Author(s)
今石 奈緒, 日高 周次, 内田 博喜, 生野 知子, 中村 優佑, 上原 幸, 清水 史明, 後藤 瑞生, 波多野 豊, 田原 康子, 嶋崎 貴信, 柴田 洋孝
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Journal Title
糖尿病
Volume: 62
Pages: 389-397
NAID
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[Journal Article] Intestinal mineralocorticoid receptor contributes to epithelial sodium channel-mediated intestinal sodium absorption and blood pressure2018
Author(s)
Nakamura T, Kurihara I, Kobayashi S, Yokota K, Murai-Takeda A, Mitsuishi Y, Morisaki M, Kohara N, Oshima Y, Minami Y, Shibata H, Itoh H
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Journal Title
J Am Heart Assoc
Volume: 7
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[Journal Article] Obesity as a key factor underlying idiopathic hyperaldosteronism2018
Author(s)
Ohno Y, Sone M, Inagaki N, Yamasaki T, Ogawa O, Takeda Y, Kurihara I, Umakoshi H, Ichijo T, Katabami T, Wada N, Ogawa Y, Yoshimoto T, Kawashima J, Watanabe M, Matsuda Y, Kobayashi H, Shibata H, Miyauchi S, Kamemura K, Fukuoka T, Yamamoto K, Otsuki M, Suzuki T, Naruse M, JPAS Study Group
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Journal Title
J Clin Endocrinol Metab
Volume: 103
Pages: 4456-4464
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[Journal Article] Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization2018
Author(s)
Mitsuishi Y, Shibata H, Kurihara I, Kobayashi S, Yokota K, Murai-Takeda A, Hayashi T, Jo R, Nakamura T, Morisaki M, Itoh H
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Journal Title
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Volume: 473
Pages: 89-99
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