The role of MRP8 as a therapeutic target in chronic kidney disease

• Project/Area Number: 15K09268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: Kuwabara Takashige 熊本大学, 大学院生命科学研究部(医), 講師 (00393356)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 慢性炎症 / MRP8 / 半月体形成性腎炎 / マクロファージ / 糸球体内クロストーク / 糸球体腎炎 / 自然炎症 / 糸球体障害 / 細胞間クロストーク

Outline of Final Research Achievements

Chronic kidney disease (CKD) is one of the most prevalent diseases and leading to the necessity of renal replacement therapy, whose novel therapeutic stratedy is eagerly awaited. We have previously reported the role of chronic inflammation in CKD as well as diabetic nephropathy. In this study, we investigated the role of MRP8, one of the inflammatory endogenous ligands, in the crescentic glomerulonephritis. Our results suggested that ablation of MRP8 in myeloid cells ameliorated crescentic glomerulonephritis through affecting macrophage polarity.MRP8 could become as a theraputic target in glomerulonephritis.

Research Products

• [Journal Article] Sirtuin 7 Deficiency Ameliorates Cisplatin-induced Acute Kidney Injury Through Regulation of the Inflammatory Response (2018)
  • Author(s): Miyasato Yoshikazu、Yoshizawa Tatsuya、Sato Yoshifumi、Nakagawa Terumasa、Miyasato Yuko、Kakizoe Yutaka、Kuwabara Takashige、Adachi Masataka、Ianni Alessandro、Braun Thomas、Komohara Yoshihiro、Mukoyama Masashi、Yamagata Kazuya
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5927-5927
  • DOI: 10.1038/s41598-018-24257-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Obesity-promoting and anti-thermogenic effects of neutrophil gelatinase-associated lipocalin in mice (2017)
  • Author(s): Ishii Akira、Katsuura Goro、Imamaki Hirotaka、Kimura Hiroyuki、Mori Keita P.、Kuwabara Takashige、Kasahara Masato、Yokoi Hideki、Ohinata Kousaku、Kawanishi Tomoko、Tsuchida Junichi、Nakamoto Yuji、Nakao Kazuwa、Yanagita Motoko、Mukoyama Masashi、Mori Kiyoshi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15501-15501
  • DOI: 10.1038/s41598-017-15825-4
  • Peer Reviewed / Open Access
• [Journal Article] A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy (2017)
  • Author(s): Guan Yu、Nakano Daisuke、Zhang Yifan、Li Lei、Liu Wenhua、Nishida Motohiro、Kuwabara Takashige、Morishita Asahiro、Hitomi Hirofumi、Mori Kiyoshi、Mukoyama Masashi、Masaki Tsutomu、Hirano Katsuya、Nishiyama Akira
  • Journal Title: J Pharmacol Sci Volume: 135 Issue: 2 Pages: 81-88
  • DOI: 10.1016/j.jphs.2017.09.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TSS-Seq analysis of low pH-induced gene expression in intercalated cells of the renal collecting duct (2017)
  • Author(s): Izumi Y
  • Journal Title: PLos One Volume: 12 Issue: 8 Pages: e0184185-e0184185
  • DOI: 10.1371/journal.pone.0184185
  • Peer Reviewed / Open Access
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A pathway counteracts glomerular injury evoked by aldosterone through p38 mitogen-activated protein kinase inhibition. (2017)
  • Author(s): Y. Kato, K. Mori, M. Kasahara, K. Osaki, A. Ishii, K.P. Mori, N. Toda, S. Ohno, T. Kuwabara, T. Tokudome, I. Kishimoto, M.A. Saleem, T. Matsusaka, K. Nakao, M. Mukoyama, M. Yanagita, H. Yokoi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 46624-46624
  • DOI: 10.1038/srep46624
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Crucial role of mesangial cell-derived connective tissue growth factor in a mouse model of anti-glomerular basement membrane glomerulonephritis. (2017)
  • Author(s): Toda N, Mori K, Kasahara M, Ishii A, Koga K, Ohno S, Mori KP. Kato Y, Osaki K, Kuwabara T, Kojima K, Taura D, Sone M, Matsusaka T, Nakao K, Mukoyama M, Yanagita M, Yokoi H.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 42114-42114
  • DOI: 10.1038/srep42114
  • NAID: 120005997757
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy. (2017)
  • Author(s): Mori KP, Yokoi H, Kasahara M, Imamaki H, Ishii A, Kuwabara T, Koga K, Kato Y, Toda N, Ohno S, Kuwahara K, Endo T, Nakao K, Yanagita M, Mukoyama M, Mori K.
  • Journal Title: J Am Soc Nephrol. Volume: 28 Issue: 1 Pages: 278-289
  • DOI: 10.1681/asn.2015101168
  • NAID: 120005820888
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. (2016)
  • Author(s): Ohno S, Yokoi H, Mori K, Kasahara M, Kuwahara K, Fujikura J, Naito M, Kuwabara T, Imamaki H, Ishii A, Saleem MA, Numata T, Mori Y, Nakao K, Yanagita M, Mukoyama M
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 27192-27192
  • DOI: 10.1038/srep27192
  • NAID: 120007100128
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease. (2016)
  • Author(s): Iwashita Y, Kuwabara T, Hayata M, Kakizoe Y, Izumi Y, Iiyama J, Kitamura K, Mukoyama M.
  • Journal Title: Am J Physiol Renal Physiol. Volume: in press Issue: 11 Pages: 1-1
  • DOI: 10.1152/ajprenal.00519.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transthyretin-related familial amyloidotic polyneuropathy found with abnormal urinalysis at a general health checkup. (2016)
  • Author(s): Yoshimura Y, Kuwabara T, Shiraishi N, Kakizoe Y, Tasaki M, Obayashi K, Ando Y, Mukoyama M.
  • Journal Title: Nephrology Volume: 21 Issue: 4 Pages: 341-2
  • DOI: 10.1111/nep.12610
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-26a inhibits TGF-β-induced extracellular matrix expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy. (2015)
  • Author(s): Koga K, Yokoi H, Mori K, Kasahara K, Kuwabara T, Imamaki H, Ishii A, Mori KP, Kato Y, Ohno S, Toda N, Saleem MA, Sugawara A, Nakao K, Yanagita M, Mukoyama M.
  • Journal Title: Diabetologia Volume: 58 Issue: 9 Pages: 2169-80
  • DOI: 10.1007/s00125-015-3642-4
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients. (2015)
  • Author(s): Imamaki H, Ishii A, Yokoi H, Kasahara M, Kuwabara T, Mori KP, Kato Y, Kuwahara T, Satoh M, Nakatani K, Saito Y, Tomosugi N, Sugawara A, Nakao K, Mukoyama M, Yanagita M, Mori K.
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: 99-106
  • DOI: 10.1371/journal.pone.0132539
  • NAID: 120005678176
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital Imaging. (2015)
  • Author(s): Nakano D, Doi K, Kitamura H, Kuwabara T, Mori K, Mukoyama M, Nishiyama A.
  • Journal Title: J Am Soc Nephrol Volume: 26 Issue: 12 Pages: 3035-44
  • DOI: 10.1681/asn.2014060577
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions. (2015)
  • Author(s): Kanda J, Mori K, Kawabata H, Kuwabara T, Mori KP, Imamaki H, Kasahara M, Yokoi H, Mizumoto C, Thoennissen NH, Koeffler HP, Barasch J, Takaori-Kondo A, Mukoyama M, Nakao K.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 1 Pages: 99-106
  • DOI: 10.1007/s10157-014-0952-7
  • NAID: 120005678175
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Local inflammatory mechanism aggravated by intraglomerular crosstalk in diabetic kidney (2017)
  • Author(s): Shuro Umemoto, Takashige Kuwabara, Daisuke Fujimoto, Tomoko Kanki, Teruhiko Mizumoto, Yutaka Kakizoe, Yuichiro Izumi, Kiyoshi Mori, Masashi Mukoyama
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Intraglomerular crosstalk in a mouse model of diabetic nephropathy aggravated by the renin-angiotensin system activation (2017)
  • Author(s): Shuro Umemoto, Takashige Kuwabara, Daisuke Fujimoto, Tomoko Kanki, Teruhiko Mizumoto, Yuichiro Izumi, Yutaka Kakizoe, Hirotaka Imamaki, Kiyoshi Mori, Masashi Mukoyama
  • Organizer: World Congress of Nephrology
  • Int'l Joint Research
• [Presentation] Myeloid-specific deletion of MRP8 ameliorates glomerulonephritis through affecting macrophage characterization. (2016)
  • Author(s): Takashige Kuwabara, Kiyoshi Mori, Manabu Hayata, Shuro Umemoto, Hideki Yokoi, Masashi Mukoyama
  • Organizer: Annual meeting 2016 of the American Society of Nephrology
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Intraglomerular crosstalk between mesangial cells and macrophages in glomerular injury. (2016)
  • Author(s): Shuro Umemoto, Takashige Kuwabara, Manabu Hayata, Daisuke Fujimoto, Tomoko Kanki, Yutaka Kakizoe, Yuichiro Izumi, Masashi Mukoyama
  • Organizer: Annual meeting 2016 of the American Society of Nephrology
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] シンポジウム ポドサイトパチーupdate 「ポドサイトとS100ファミリー分子」 (2016)
  • Author(s): 桒原孝成、梅本周郎、向山政志
  • Organizer: 第46回日本腎臓学会西部学術大会
  • Place of Presentation: シーガイアコンベンションセンター、宮崎
  • Year and Date: 2016-10-14
  • Invited
• [Presentation] The role of activated renin-angiotensin system for the MRP8/TLR4 signaling in diabetic nephropathy. (2016)
  • Author(s): Shuro Umemoto, Takashige Kuwabara, Hirotaka Imamaki, Manabu Hayata, Yuichiro Izumi, Yutaka Kakizoe, Kiyoshi Mori, Masashi Mukoyama
  • Organizer: The 26th Scientific Meeting of the International Society of Hypertension.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-09-24
  • Int'l Joint Research
• [Presentation] 糖尿病マウスにおけるレニン・アンジオテンシン系亢進がMRP8/TLR4シグナルに与える影響およびその機序の検討 (2015)
  • Author(s): 桒原孝成、今牧博貴、森 潔、横井秀基, 向山政志
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛、ひめぎんホール
  • Year and Date: 2015-10-10
• [Presentation] 腎疾患および透析患者における慢性炎症の意義 ～レニン・アンジオテンシン系阻害薬の効果と合わせて～ (2015)
  • Author(s): 桒原孝成
  • Organizer: 第21回日本HDF研究会学術総会
  • Place of Presentation: 熊本、ホテル日航熊本
  • Year and Date: 2015-09-26
  • Invited
• [Presentation] 骨髄細胞特異的MRP8欠損はマクロファージ形質を変化させることで糸球体腎炎を軽減する (2015)
  • Author(s): 桒原孝成、森 潔、横井秀基、笠原正登、柳田素子、向山政志
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-06-05
• [Book] 腎疾患研究の最新の話題 (2017)
  • Author(s): 桒原孝成、向山政志
  • Total Pages: 2
  • Publisher: 北隆館
• [Book] 特集 腎と老化「老化と体液量調節機構」 (2016)
  • Author(s): 桒原孝成、向山政志
  • Total Pages: 4
  • Publisher: 科学評論社
• [Book] 主治医として診る高血圧診療「BNP, NT-proBNP」 (2016)
  • Author(s): 桒原孝成、向山政志
  • Total Pages: 5
  • Publisher: 医学書院
• [Book] 肥満関連腎臓病 (2016)
  • Author(s): 桒原孝成、向山政志
  • Total Pages: 5
  • Publisher: 科学評論社
• [Remarks] 熊本大学腎臓内科HP
• [Remarks] 熊本大学腎臓内科HP
  • URL: http://www.kumadai-nephrology.com/