母児概日リズム同期と次世代疾患感受性の多層多元的代謝リズムパネルからの理解

• Project/Area Number: 21K18270
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Keio University
• Principal Investigator: 伊藤 裕 慶應義塾大学, 医学部(信濃町), 特任教授 (40252457)
• Co-Investigator(Kenkyū-buntansha): 入江 潤一郎 慶應義塾大学, 医学部(信濃町), 准教授 (70306687) ; 宮下 和季 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (50378759) ; 木内 謙一郎 慶應義塾大学, 医学部(信濃町), 講師 (50528578)
• Project Period (FY): 2021-07-09 – 2026-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000); Fiscal Year 2025: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2024: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2023: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 概日リズム / 母児連関 / 液性因子 / 内分泌代謝 / 糖尿病 / 慢性腎臓病

Outline of Research at the Start

概日時計は、変動する環境に対し予測的に適応する生体恒常性維持機構である。昼夜の明暗や摂食空腹リズムに同調し、概日リズムを作り出している。シフトワークなどにより生じる概日リズム障害は、糖尿病や心血管病の危険因子であることが疫学的に知られている。しかし、母体の概日リズムが、胎児の発達および児の成育と将来の疾患感受性に与える影響は明らかではない。本研究では、妊娠母体の概日リズム障害が、胎盤を通過する液性因子のリズム変調を介して、腎臓や膵臓の形成、および、その後の疾患感受性を決定すると仮説し、母児間のリズム同調不全が仔の疾病発症に与える影響を、独自の「代謝リズムパネル」を構築し、多層多元的に解明する。

Outline of Annual Research Achievements

概日時計は、変動する環境に対し予測的に生体活動を適応させる生体恒常性維持機構であり、昼夜の明暗リズムを基盤に、摂食と空腹、睡眠と覚醒などによって修飾され、概日リズムを作り出している。妊娠中の母体においても概日リズムの維持は、安定した周産期と児の成育に重要であると考えられ、実際にシフトワーカーの妊婦では低出生体重児が多いことが報告されている。しかし、母体の概日リズムが、胎児の発達および児の成育と将来の疾患感受性に与える詳細な影響は明らかではない。そこで本研究では、妊娠母体の概日リズム障害が、胎盤を通過する液性因子のリズム変調を介して、臓器形成、および、その後の疾患感受性を決定すると仮説を立て、液性因子を介した母児間のリズム獲得不全が仔の疾病発症に与える影響を、「代謝リズムパネル」を駆使して、多層多元的に解明することを目的としている。
C５７BL/６マウスを妊娠期間中のみ、12時間明暗周期の環境下または、５日に１回、８時間位相を早めるサイクル（Continuous Phase Shift: CPS）で飼育した。両群の出産個体数に有意差は認められなかったが、出生直後の児の体重は、CPS群で有意に低下していた。体重は3週以降で同等となり、オスの児を生後４週から１２週にわたり、12時間明暗周期の環境下で低脂肪食負荷を行ったところ、対照群とCPS群の間に体重、脂肪重量、肝臓重量、糖負荷試験による耐糖能に有意差は認められなかったが、高脂肪食負荷を行ったところ、肥満が増悪し、耐糖能が悪化した。児の肝臓のメタボローム解析とトランスクリプトーム解析を行ったところ、CPS群の児に高脂肪食を負荷を行った群でのみ振動する代謝産物、遺伝子は脂質代謝に関わるものが多く含まれていた。また、母体概日時計を妊娠中に欠損させた場合も、児が高脂肪食負荷によって肥満が増悪し、耐糖能が悪化した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

動物実験モデルの作成やサンプリングは順調に進んでいるほか、トランスクリプトーム解析やメタボローム解析、シングルセルRNA-seqも進んでおり、妊娠中母体の概日リズム異常による仔への表現型も観察されているため。

Strategy for Future Research Activity

今後、網羅的リズム情報をパネル化した代謝リズムパネルを作成するため、仔の肝臓のトランスクリプトーム、メタボローム解析などを進めるほか、妊娠中の母体と胎児の肝臓のトランスクリプトーム解析や胎盤のシングルRNA-seq解析も行い、母児間の同期現象や脱同調による臓器発達への影響を検討していく予定である。また、時間制限食やカロリー制限により、児の肥満が改善するか検討する。

Research Products

• [Journal Article] Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men (2024)
  • Author(s): Yamaguchi Shintaro、Irie Junichiro、Mitsuishi Masanori、Uchino Yuichi、Nakaya Hideaki、Takemura Ryo、Inagaki Emi、Kosugi Shotaro、Okano Hideyuki、Yasui Masato、Tsubota Kazuo、Hayashi Kaori、Yoshino Jun、Itoh Hiroshi
  • Journal Title: Endocrine Journal Volume: 71 Issue: 2 Pages: 153-169
  • DOI: 10.1507/endocrj.EJ23-0431
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Podocyte Ercc1 is indispensable for glomerular integrity (2024)
  • Author(s): Hama Eriko Yoshida、Nakamichi Ran、Hishikawa Akihito、Kihara Miho、Abe Takaya、Yoshimoto Norifumi、Nishimura Erina Sugita、Itoh Hiroshi、Hayashi Kaori
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 704 Pages: 149713-149713
  • DOI: 10.1016/j.bbrc.2024.149713
  • Peer Reviewed
• [Journal Article] Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism (2023)
  • Author(s): Yamaguchi Shintaro、Kojima Daiki、Iqbal Tooba、Kosugi Shotaro、Franczyk Michael P.、Qi Nathan、Sasaki Yo、Yaku Keisuke、Kaneko Kenji、Kinouchi Kenichiro、Itoh Hiroshi、Hayashi Kaori、Nakagawa Takashi、Yoshino Jun
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 674 Pages: 162-169
  • DOI: 10.1016/j.bbrc.2023.07.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease. (2023)
  • Author(s): Nakayama T, Yamaguchi S (corresponding author), Hayashi K, Uchiyama K, Tajima T, Azegami T, Morimoto K, Yoshida T, Yoshino J, Monkawa T, Kanda T, Itoh H.
  • Journal Title: Frontiers in Medicine (Lausanne) Volume: 10 Pages: 1137981-1137981
  • DOI: 10.3389/fmed.2023.1137981
  • Peer Reviewed
• [Journal Article] Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection (2023)
  • Author(s): Nakayama Takashin、Azegami Tatsuhiko、Kiso Maki、Imai Masaki、Uraki Ryuta、Hayashi Kaori、Hishikawa Akihito、Yoshimoto Norifumi、Nakamichi Ran、Sugita-Nishimura Erina、Yoshida-Hama Eriko、Kawaoka Yoshihiro、Itoh Hiroshi
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 3103-3103
  • DOI: 10.1038/s41598-023-30305-8
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of a telemedicine system in subjects with gestational diabetes mellitus (TELEGLAM): Study protocol for a randomized controlled trial (2023)
  • Author(s): Aoyama Kazuki、Nakajima Yuya、Meguro Shu、Sato Yasunori、Goto Rei、Hida Mariko、Arimitsu Takeshi、Kasuga Yoshifumi、Tanaka Mamoru、Itoh Hiroshi
  • Journal Title: Heliyon Volume: 9 Issue: 11 Pages: e22504-e22504
  • DOI: 10.1016/j.heliyon.2023.e22504
• [Journal Article] N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) has potent anti-fibrotic and anti-inflammatory activity in a fibrotic kidney model: is it an old uremic toxin? (2023)
  • Author(s): Yoshimura Norito、Yamada Katsutoshi、Ono Takashi、Notoya Mitsuru、Yukioka Hideo、Takahashi Rina、Wakino Shu、Kanda Takeshi、Itoh Hiroshi
  • Journal Title: Clinical and Experimental Nephrology Volume: 27 Issue: 11 Pages: 901-911
  • DOI: 10.1007/s10157-023-02379-1
• [Journal Article] Comparison of the effects of angiotensin receptor?neprilysin inhibitors and thiazide diuretic/renin?angiotensin system inhibitor combination therapy in hypertensive patients: a retrospective cohort study (2023)
  • Author(s): Mitsuno Ryunosuke、Uchiyama Kiyotaka、Nakayama Takashin、Takahashi Rina、Yoshimoto Norifumi、Yamaguchi Shintaro、Washida Naoki、Kanda Takeshi、Hayashi Kaori、Itoh Hiroshi
  • Journal Title: Journal of Human Hypertension Volume: 37 Issue: 12 Pages: 1049-1055
  • DOI: 10.1038/s41371-023-00851-9
  • Peer Reviewed
• [Journal Article] Seasonal variation in predialysis systolic blood pressure and cardiovascular events in patients on maintenance hemodialysis (2023)
  • Author(s): Takahashi Rina、Maruki Tomomi、Uchiyama Kiyotaka、Washida Naoki、Shibagaki Keigo、Yanai Akane、Nakayama Takashin、Hayashi Kaori、Kanda Takeshi、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 46 Issue: 9 Pages: 2192-2202
  • DOI: 10.1038/s41440-023-01364-1
• [Journal Article] Longitudinal changes in pancreatic volume and pancreatic fat with weight gain in Japanese without diabetes: An analysis using health check-up data (2023)
  • Author(s): Sunouchi Maria、Inaishi Jun、Shimizu-Hirota Ryoko、Saisho Yoshifumi、Hayashi Kaori、Takaishi Hiromasa、Itoh Hiroshi
  • Journal Title: Metabolism Open Volume: 19 Pages: 100250-100250
  • DOI: 10.1016/j.metop.2023.100250
• [Journal Article] Intermittent Fasting Sustainably Improves Glucose Tolerance in Normal Weight Male Mice Through Histone Hyperacetylation (2023)
  • Author(s): Endo Sho、Uto Asuka、Miyashita Kazutoshi、Sato Masaaki、Inoue Hiroyuki、Fujii Kentaro、Hagiwara Aika、Ryuzaki Masaki、Oshida Takuma、Kinouchi Kenichiro、Itoh Hiroshi
  • Journal Title: Journal of the Endocrine Society Volume: 7 Issue: 7
  • DOI: 10.1210/jendso/bvad082
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A systematic review and meta-analysis of the clinical impact of stopping renin?angiotensin system inhibitor in patients with chronic kidney disease (2023)
  • Author(s): Nakayama Takashin、Mitsuno Ryunosuke、Azegami Tatsuhiko、Sato Yasunori、Hayashi Kaori、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 46 Issue: 6 Pages: 1525-1535
  • DOI: 10.1038/s41440-023-01260-8
• [Journal Article] DNA-damaged podocyte-CD8 T?cell crosstalk exacerbates kidney injury by altering DNA methylation (2023)
  • Author(s): Nakamichi Ran、Hishikawa Akihito、Chikuma Shunsuke、Yoshimura Akihiko、Sasaki Takashi、Hashiguchi Akinori、Abe Takaya、Tokuhara Tomoko、Yoshimoto Norifumi、Nishimura Erina Sugita、Hama Eriko Yoshida、Azegami Tatsuhiko、Nakayama Takashin、Hayashi Kaori、Itoh Hiroshi
  • Journal Title: Cell Reports Volume: 42 Issue: 4 Pages: 112302-112302
  • DOI: 10.1016/j.celrep.2023.112302
  • Peer Reviewed / Open Access
• [Journal Article] NAD+ and mtRNA sensing drive human kidney diseases (2023)
  • Author(s): Itoh Hiroshi、Yoshino Jun
  • Journal Title: Nature Metabolism Volume: 5 Issue: 3 Pages: 357-359
  • DOI: 10.1038/s42255-023-00762-6
  • Peer Reviewed
• [Journal Article] Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression (2023)
  • Author(s): Yoichi Oshima, Shu Wakino, Takeshi Kanda, Takaya Tajima, Tomoaki Itoh, Kiyotaka Uchiyama, Keiko Yoshimoto, Jumpei Sasabe, Masato Yasui, Hiroshi Itoh
  • Journal Title: Sci Rep Volume: 13 Issue: 1 Pages: 3331-3331
  • DOI: 10.1038/s41598-023-30056-6
  • Peer Reviewed / Open Access
• [Journal Article] Host metabolic benefits of prebiotic exopolysaccharides produced by Leuconostoc mesenteroides (2023)
  • Author(s): Miyamoto Junki、Shimizu Hidenori、Hisa Keiko、Matsuzaki Chiaki、Inuki Shinsuke、Ando Yuna、Nishida Akari、Izumi Ayano、Yamano Mayu、Ushiroda Chihiro、Irie Junichiro、Katayama Takane、Ohno Hiroaki、Itoh Hiroshi、Yamamoto Kenji、Kimura Ikuo
  • Journal Title: Gut Microbes Volume: 15 Issue: 1 Pages: 2161271-2161271
  • DOI: 10.1080/19490976.2022.2161271
  • Peer Reviewed / Open Access
• [Journal Article] Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification (2022)
  • Author(s): Jo Rie、Shibata Hirotaka、Kurihara Isao、Yokota Kenichi、Kobayashi Sakiko、Murai-Takeda Ayano、Mitsuishi Yuko、Hayashi Takeshi、Nakamura Toshifumi、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 46 Issue: 1 Pages: 19-31
  • DOI: 10.1038/s41440-022-01036-6
  • Peer Reviewed
• [Journal Article] Increased alpha cell to beta cell ratio in patients with pancreatic cancer (2022)
  • Author(s): Tsuchiya Tami、Saisho Yoshifumi、Inaishi Jun、Sasaki Hironobu、Sato Midori、Nishikawa Masaru、Masugi Yohei、Yamada Taketo、Itoh Hiroshi
  • Journal Title: Endocrine Journal Volume: 69 Issue: 12 Pages: 1407-1414
  • DOI: 10.1507/endocrj.EJ22-0170
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Vaccination against connective tissue growth factor attenuates the development of renal fibrosis. (2022)
  • Author(s): Nakayama T, Azegami T, Hayashi K, Hishikawa A, Yoshimoto N, Nakamichi R, Sugita E, Itoh H
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 10933-10933
  • DOI: 10.1038/s41598-022-15118-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage (2022)
  • Author(s): Ida-Naitoh Makiko、Tokuyama Hirobumi、Futatsugi Koji、Yasuda Marie、Adachi Keika、Kanda Takeshi、Tanabe Yoshiyuki、Wakino Shu、Itoh Hiroshi
  • Journal Title: Kidney International Volume: 102 Issue: 4 Pages: 798-814
  • DOI: 10.1016/j.kint.2022.05.018
  • Peer Reviewed
• [Journal Article] The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease (2022)
  • Author(s): Takahashi R, Kanda T, Komatsu M, Itoh T, Minakuchi H, Urai H, Kuroita T, Shigaki S, Tsukamoto T, Higuchi N, Ikeda M, Yamanaka R, Yoshimura N, Ono T, Yukioka H, Hasegawa K, Tokuyama H, Wakino S, Itoh H.
  • Journal Title: Sci Rep Volume: 12(1) Issue: 1 Pages: 6398-6399
  • DOI: 10.1038/s41598-022-10476-6
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal epithelial NAD(+) biosynthesis regulates GLP-1 production and postprandial glucose metabolism in mice (2022)
  • Author(s): Nagahisa Taichi, Yamaguchi Shintaro, Kosugi Shotaro, Homma Koichiro, Miyashita Kazutoshi, Irie Junichiro, Yoshino Jun, Itoh Hiroshi
  • Journal Title: Endocrinology Volume: 163 Issue: 4 Pages: 1-12
  • DOI: 10.1210/endocr/bqac023
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor (2022)
  • Author(s): Kohata Nao、Kurihara Isao、Yokota Kenichi、Kobayashi Sakiko、Murai-Takeda Ayano、Mitsuishi Yuko、Nakamura Toshifumi、Morisaki Mitsuha、Kozuma Takahide、Torimitsu Takuto、Kawai Miki、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 45 Issue: 4 Pages: 641-649
  • DOI: 10.1038/s41440-022-00859-7
  • Peer Reviewed / Open Access
• [Journal Article] Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes (2021)
  • Author(s): Sasaki Hironobu、Saisho Yoshifumi、Inaishi Jun、Watanabe Yuusuke、Tsuchiya Tami、Makio Masayoshi、Sato Midori、Nishikawa Masaru、Kitago Minoru、Yamada Taketo、Itoh Hiroshi
  • Journal Title: Diabetologia Volume: 64 Issue: 8 Pages: 1816-1821
  • DOI: 10.1007/s00125-021-05467-7
  • Peer Reviewed
• [Journal Article] Association between testosterone and lipid profiles under statin therapy and its clinical impact on the cardiovascular event risk (2021)
  • Author(s): Nakayama Atsuko、Morita Hiroyuki、Kawahara Takuya、Itoh Hiroshi、Komuro Issei
  • Journal Title: Heart and Vessels Volume: 36 Issue: 12 Pages: 1794-1803
  • DOI: 10.1007/s00380-021-01872-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability (2021)
  • Author(s): Ikeda Shota、Shinohara Keisuke、Enzan Nobuyuki、Matsushima Shouji、Tohyama Takeshi、Funakoshi Kouta、Kishimoto Junji、Itoh Hiroshi、Komuro Issei、Tsutsui Hiroyuki
  • Journal Title: Journal of Hypertension Volume: 39 Issue: 7 Pages: 1435-1443
  • DOI: 10.1097/hjh.0000000000002823
  • Peer Reviewed
• [Journal Article] Association of visit‐to‐visit glycemic variability with risk of cardiovascular diseases in high‐risk Japanese patients with type 2 diabetes: A subanalysis of the EMPATHY trial (2021)
  • Author(s): Sato Midori、Inaishi Jun、Saisho Yoshifumi、Sato Yasunori、Komuro Issei、Itoh Hiroshi
  • Journal Title: Journal of Diabetes Investigation Volume: 12 Issue: 12 Pages: 2190-2196
  • DOI: 10.1111/jdi.13597
  • Peer Reviewed
• [Journal Article] Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy. (2021)
  • Author(s): Yasuda I, Hasegawa K, Sakamaki Y, Muraoka H, Kawaguchi T, Kusahana E, Ono T, Kanda T, Tokuyama H, Wakino S, Itoh H.
  • Journal Title: J Am Soc Nephrol Volume: 11 Issue: 6 Pages: 1355-1370
  • DOI: 10.1681/asn.2020081188
  • Peer Reviewed
• [Journal Article] Clinical utility of 1‐month postpartum random plasma glucose and glycated hemoglobin combined with pre‐pregnancy body mass index for detecting postpartum glucose intolerance in Japanese women with gestational diabetes (2021)
  • Author(s): Sugiyama Kazutoshi、Saisho Yoshifumi、Kasuga Yoshifumi、Ochiai Daigo、Itoh Hiroshi
  • Journal Title: Journal of Diabetes Investigation Volume: 12 Issue: 12 Pages: 2242-2246
  • DOI: 10.1111/jdi.13612
  • Peer Reviewed
• [Journal Article] Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians (2021)
  • Author(s): Yuko Sato, Koji Atarashi, Damian R. Plichta, Yasumichi Arai, Satoshi Sasajima, SM. Kearney, Kozue Takeshita, AN. Skelly, Youxian Li, Takeshi Tanoue, Seiko Narushima, DR. Littman, MA. Fischbach, Y Uwamino, T Inoue, A Honda, Masahira Hattori, Tsuyoshi Murai, Ramnik J. Xavier, Nobuyoshi Hirose, Kenya Honda, et al.
  • Journal Title: Nature Volume: 599 Issue: 7885 Pages: 458-464
  • DOI: 10.1038/s41586-021-03832-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression (2021)
  • Author(s): Shiizaki Kazuhiro、Tsubouchi Asako、Miura Yutaka、....Itoh Hiroshi、....Kuro-o Makoto
  • Journal Title: Journal of Clinical Investigation Volume: 131 Issue: 16
  • DOI: 10.1172/jci145693
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic alterations in podocytes in diabetic nephropathy. (2021)
  • Author(s): Sugita E, Hayashi K (corresponding author), Hishikawa A, Itoh H.
  • Journal Title: Front Pharmacol, Volume: 12 Pages: 759299-759299
  • DOI: 10.3389/fphar.2021.759299
  • Peer Reviewed / Open Access
• [Journal Article] Circadian rhythms in the tissue-specificity from metabolism to immunity: insights from omics studies (2021)
  • Author(s): Kinouchi Kenichiro、Mikami Yohei、Kanai Takanori、Itoh Hiroshi
  • Journal Title: Molecular Aspects of Medicine Volume: 80 Pages: 100984-100984
  • DOI: 10.1016/j.mam.2021.100984
  • Peer Reviewed
• [Journal Article] Revisiting Regulators of Human β-cell Mass to Achieve β-cell?centric Approach Toward Type 2 Diabetes (2021)
  • Author(s): Sasaki Hironobu、Saisho Yoshifumi、Inaishi Jun、Itoh Hiroshi
  • Journal Title: Journal of the Endocrine Society Volume: 5 Issue: 10 Pages: 1-14
  • DOI: 10.1210/jendso/bvab128
  • Peer Reviewed
• [Journal Article] DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation (2021)
  • Author(s): Akihito Hishikawa, Kaori Hayashi (corresponding author), Akiko Kubo, Kazutoshi Miyashita, Akinori Hashiguchi, Kenichiro Kinouchi, Norifumi Yoshimoto, Ran Nakamichi, Riki Akashio, Erina Sugita, Tatsuhiko Azegami, Toshiaki Monkawa, Makoto Suematsu, Hiroshi Itoh.
  • Journal Title: iScience. Volume: 24(12) Issue: 12 Pages: 103436-103436
  • DOI: 10.1016/j.isci.2021.103436
  • Peer Reviewed / Open Access
• [Journal Article] Vaccination against receptor for advanced glycation end products attenuates the progression of diabetic kidney disease. (2021)
  • Author(s): Azegami T, Nakayama T, Hayashi K, Hishikawa A, Yoshimoto N, Nakamichi R, Itoh H.
  • Journal Title: Diabetes. Volume: 70(9) Issue: 9 Pages: 2147-2158
  • DOI: 10.2337/db20-1257
  • Peer Reviewed / Open Access
• [Journal Article] Effect of esaxerenone on nocturnal blood pressure and natriuretic peptide in different dipping phenotypes (2021)
  • Author(s): Kario Kazuomi、Ito Sadayoshi、Itoh Hiroshi、Rakugi Hiromi、Okuda Yasuyuki、Yamakawa Satoru
  • Journal Title: Hypertension Research Volume: 45 Issue: 1 Pages: 97-105
  • DOI: 10.1038/s41440-021-00756-5
  • Peer Reviewed
• [Journal Article] Seasonal variation and predictors of intradialytic blood pressure decline: a retrospective cohort study (2021)
  • Author(s): Uchiyama Kiyotaka、Shibagaki Keigo、Yanai Akane、Kusahana Ei、Nakayama Takashin、Morimoto Kohkichi、Washida Naoki、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 44 Issue: 11 Pages: 1417-1427
  • DOI: 10.1038/s41440-021-00714-1
  • Peer Reviewed
• [Journal Article] Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice With Histone Acetylation in <i>Dpp-4</i> Promoter (2021)
  • Author(s): Uto Asuka、Miyashita Kazutoshi、Endo Sho、Sato Masaaki、Ryuzaki Masaki、Kinouchi Kenichiro、Mitsuishi Masanori、Meguro Shu、Itoh Hiroshi
  • Journal Title: Endocrinology Volume: 162 Issue: 12
  • DOI: 10.1210/endocr/bqab193
  • Peer Reviewed
• [Journal Article] Home‐based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial (2021)
  • Author(s): Uchiyama Kiyotaka、Adachi Keika、Muraoka Kaori、Nakayama Takashin、Oshida Takuma、Yasuda Marie、Hishikawa Akihito、Minakuchi Hitoshi、Miyashita Kazutoshi、Tokuyama Hirobumi、Wakino Shu、Itoh Hiroshi
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle Volume: 12 Issue: 6 Pages: 1789-1802
  • DOI: 10.1002/jcsm.12775
  • Peer Reviewed
• [Journal Article] Activation of the intestinal tissue renin-angiotensin system by transient sodium loading in salt-sensitive rats (2021)
  • Author(s): Ryuzaki Masaki、Miyashita Kazutoshi、Sato Masaaki、Inoue Hiroyuki、Fujii Kentaro、Hagiwara Aika、Uto Asuka、Endo Sho、Oshida Takuma、Kinouchi Kenichiro、Itoh Hiroshi
  • Journal Title: Journal of Hypertension Volume: 40 Issue: 1 Pages: 33-45
  • DOI: 10.1097/hjh.0000000000002974
  • Peer Reviewed / Open Access
• [Journal Article] CASZ1b is a novel transcriptional corepressor of mineralocorticoid receptor (2020)
  • Author(s): Yokota Kenichi、Shibata Hirotaka、Kurihara Isao、Kobayashi Sakiko、Murai-Takeda Ayano、Itoh Hiroshi
  • Journal Title: Hypertension Research Volume: 44 Issue: 4 Pages: 407-416
  • DOI: 10.1038/s41440-020-00562-5
  • Peer Reviewed