神田 武志 (カンダ タケシ)

Kanda, Takeshi

写真a

所属(所属キャンパス)

医学部 内科学教室(腎臓・内分泌・代謝) (信濃町)

職名

専任講師(有期)

外部リンク

 

研究分野 【 表示 / 非表示

  • 腎臓内科学

 

論文 【 表示 / 非表示

  • Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

    Muraoka H., Hasegawa K., Sakamaki Y., Minakuchi H., Kawaguchi T., Yasuda I., Kanda T., Tokuyama H., Wakino S., Itoh H.

    Cell Reports (Cell Reports)  27 ( 1 ) 199 - 212.e5 2019年04月

     概要を見る

    © 2019 The Author(s) Nicotinamide adenine dinucleotide (NAD + ) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD + precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy. The expression of Nampt in PTs was downregulated in streptozotocin (STZ)-treated diabetic mice when they exhibited albuminuria. This albuminuria was ameliorated in PT-specific Nampt-overexpressing transgenic (TG) mice. PT-specific Nampt-conditional knockout (Nampt CKO) mice exhibited TBM thickening and collagen deposition, which were associated with the upregulation of the profibrogenic gene TIMP-1. Nampt CKO mice also exhibited the downregulation of sirtuins, particularly in Sirt6. PT-specific Sirt6-knockout mice exhibited enhanced fibrotic phenotype resembling that of Nampt CKO mice with increased Timp1 expression. In conclusion, the Nampt-Sirt6 axis in PTs serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. Muraoka et al. reveal that the Nampt-Sirt6 axis in proximal tubules serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy.

  • Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes

    Hishikawa A., Hayashi K., Abe T., Kaneko M., Yokoi H., Azegami T., Nakamura M., Yoshimoto N., Kanda T., Sakamaki Y., Itoh H.

    Cell Reports (Cell Reports)  26 ( 5 ) 1318 - 1332.e4 2019年01月

     概要を見る

    © 2019 The Author(s) Hishikawa et al. reveal that KAT5-mediated DNA repair is essential for podocyte maintenance and is related to changes in DNA methylation status. Decreased podocyte KAT5 expression may contribute to the pathophysiology of diabetic nephropathy, suggesting a therapeutic target.

  • β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects

    Tajima T., Yoshifuji A., Matsui A., Itoh T., Uchiyama K., Kanda T., Tokuyama H., Wakino S., Itoh H.

    Kidney International (Kidney International)  2019年

    ISSN  00852538

     概要を見る

    © 2019 International Society of Nephrology Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of β-OHB using an osmotic mini-pump before and after IRI. We also tested the effects of increasing endogenous serum β-OHB levels by fasting. Renal IRI was attenuated by β-OHB treatment compared to saline control, with similar results in the fasting condition. β-OHB treatment reduced the number of terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL)-positive cells and increased expression of forkhead transcription factor O3 (FOXO3), an upstream regulator of pyroptosis. Although β-OHB treatment did not impact markers of apoptosis, it decreased the expression of caspase-1 and proinflammatory cytokines, indicating that β-OHB blocked pyroptosis. In a human proximal tubular cell line exposed to hypoxia and reoxygenation, β-OHB reduced cell death in a FOXO3-dependent fashion. Histone acetylation was decreased in kidneys exposed to IRI and in proximal tubular cells exposed to hypoxia and reoxygenation, and this effect was ameliorated by β-OHB through the inactivation of histone deacetylases. In vitro, β-OHB treatment restored histone acetylation at the FOXO3 promoter. Consistent with epigenetic molecular effects, the renoprotective effects of β-OHB were still observed when the continuous infusion was stopped at the time of IRI. Thus, β-OHB attenuates renal IRI through anti-pyroptotic effects, likely mediated by an epigenetic effect on FOXO3 expression.

  • 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)  2019年

    ISSN  09169636

     概要を見る

    © 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.

  • NNMT activation can contribute to the development of fatty liver disease by modulating the NAD <sup>+</sup> metabolism

    Komatsu M., Kanda T., Urai H., Kurokochi A., Kitahama R., Shigaki S., Ono T., Yukioka H., Hasegawa K., Tokuyama H., Kawabe H., Wakino S., Itoh H.

    Scientific Reports (Scientific Reports)  8 ( 1 )  2018年12月

     概要を見る

    © 2018 The Author(s). Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide and S-adenosylhomocysteine. Recently, this enzyme has also been reported to modulate hepatic nutrient metabolism, but its role in the liver has not been fully elucidated. We developed transgenic mice overexpressing NNMT to elucidate its role in hepatic nutrient metabolism. When fed a high fat diet containing NAM, a precursor for nicotinamide adenine dinucleotide (NAD)+, these NNMT-overexpressing mice exhibit fatty liver deterioration following increased expression of the genes mediating fatty acid uptake and decreased very low-density lipoprotein secretion. NNMT overactivation decreased the NAD+ content in the liver and also decreased gene activity related to fatty acid oxidation by inhibiting NAD+-dependent deacetylase Sirt3 function. Moreover, the transgenic mice showed liver fibrosis, with the induction of inflammatory and fibrosis genes. Induced NNMT expression decreased the tissue methylation capacity, thereby reducing methylation of the connective tissue growth factor (CTGF) gene promoter, resulting in increased CTGF expression. These data indicate that NNMT links the NAD+ and methionine metabolic pathways and promotes liver steatosis and fibrosis. Therefore, targeting NNMT may serve as a therapeutic strategy for treating fatty liver and fibrosis.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • アンジオテンシン抑制による蛋白尿減少作用の経時的比較検討

    林晃一,本間康一郎,神田武志,猿田享男

    第22回日本臨床薬理学会総会, 2001年12月

  • 食塩感受性ラットの腎微小循環における酸化ストレスの役割

    神田武志,林晃一,本間康一郎,小澤裕理,大久保建,高松一郎,立松覚,猿田享男

    第5回日本心血管内分泌代謝学会総会, 2001年11月

  • アンジオテンシン受容体拮抗薬の抗蛋白尿作用と降圧作用との関連

    本間康一郎,林晃一,小澤裕理,松田洋人,大久保建,高松一郎,神田武志,猿田享男

    第24回日本高血圧学会総会, 2001年10月

  • Role of T-type calcium channels as a determinant of glomerular microcirculation and subsequent renal protection

    Kanda Takeshi, Hayashi Koichi, Ozawa Yuri, Nagahama Takahiko, Homma Koichiro, Tokuyama Hirobumi, Okubo Ken, Takamatsu Ichiro, Saruta Takao

    Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 2001年10月

  • T型ならびにL型カルシウム拮抗薬の腎保護作用と微小循環作用との直接的検討

    神田武志,林晃一,本間康一郎,徳山博文,大久保建,高松一郎,長浜貴彦,猿田享男

    第24回日本高血圧学会総会, 2001年10月

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競争的資金等の研究課題 【 表示 / 非表示

  • 慢性腎臓病の動脈硬化進展におけるNAD代謝産物の役割

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 神田 武志, 基盤研究(C), 補助金,  代表

  • 内分泌ホルモンによる内皮機能に基づいた脂肪機能制御

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 神田 武志, 基盤研究(C), 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • 内科学(腎臓・内分泌・代謝)講義

    2020年度

  • 内科学講義

    2020年度

  • 内科学講義

    2019年度

  • 内科学(腎臓・内分泌・代謝)講義

    2019年度