炎症メディエーターMRP8が腎炎進展に果たす役割の検討

2019 Fiscal Year Research-status Report

• Project/Area Number: 19K08728
• Research Institution: Kumamoto University
• Principal Investigator: 桑原 孝成 熊本大学, 大学院生命科学研究部(医), 講師 (00393356)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マクロファージ / GBM腎炎 / MRP8 / Mincle

Outline of Annual Research Achievements

2019年度はMRP8欠損骨髄由来細胞特異的レポーターマウスを用いて、糸球体腎炎惹起時の骨髄由来細胞の特性を解析した。その結果、MRP8の欠損はマクロファージのM1形質に重要な役割を果たすmacrophage-inducible C-type lectin (Mincle)発現に影響を与えていることが明らかとなった。具体的には、末梢血の解析では健常時、腎炎時に関わらず好中球のMincle発現を抑制していた。単離糸球体の解析においては末梢血同様、好中球のMincle発現を常時抑制する一方、マクロファージ分画では腎炎時に発現増加するMincleを抑制することが示された。その機序は不明な点が多いが、細胞質内Ca結合蛋白であるMRP8は炎症誘導時にCa依存性C-type lectinの一つであるLセレクチンの切断、細胞膜表面への移動に関与することが報告されている。腎炎での糸球体局所炎症誘導時にMRP8が浸潤マクロファージ上のMincle発現に重要な可能性も考えられる。当該年度の研究結果により一定の成果が得られたため、論文として報告した。さらに計画書記載の患者サンプルを用いた検討についても血液透析患者血清MRP8濃度と予後予測について関連性を示唆する結果が得られており、論文投稿を行った。

Current Status of Research Progress

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

Reason

当該年度までの検討結果について論文報告を行うことができた。引き続き臨床応用を念頭に置いた研究を進めていく。

Strategy for Future Research Activity

2019年までの検討結果について論文報告を行った。次のステップとして臨床応用を目指した計画を大阪大学のグループと共同ですでに開始している

Research Products

• [Journal Article] Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk (2020)
  • Author(s): Hata Yusuke、Kuwabara Takashige、Mori Kiyoshi、Kan Youngna、Sato Yuki、Umemoto Shuro、Fujimoto Daisuke、Kanki Tomoko、Nishiguchi Yoshihiko、Yokoi Hideki、Kakizoe Yutaka、Izumi Yuichiro、Yanagita Motoko、Mukoyama Masashi
  • Journal Title: Scientific Reports Volume: 10 Pages: 3056
  • DOI: 10.1038/s41598-020-59970-9
• [Journal Article] The predictive role of serum calprotectin on mortality in hemodialysis patients with high phosphoremia (2020)
  • Author(s): Kanki Tomoko、Kuwabara Takashige、Morinaga Jun、Fukami Hirotaka、Umemoto Shuro、Fujimoto Daisuke、Mizumoto Teruhiko、Hayata Manabu、Kakizoe Yutaka、Izumi Yuichiro、Tajiri Saeko、Tajiri Tetsuya、Kitamura Kenichiro、Mukoyama Masashi
  • Journal Title: BMC Nephrology Volume: 21 Pages: in press
  • DOI: 10.1186/s12882-020-01812-x
• [Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study (2019)
  • Author(s): Morinaga Jun、Kakuma Tatsuyuki、Fukami Hirotaka、Hayata Manabu、Uchimura Kohei、Mizumoto Teruhiko、Kakizoe Yutaka、Miyoshi Taku、Shiraishi Naoki、Adachi Masataka、Izumi Yuichiro、Kuwabara Takashige, et al.
  • Journal Title: Nephrology Dialysis Transplantation Volume: 35 Pages: 854～860
  • DOI: 10.1093/ndt/gfz236
• [Journal Article] Regression of hepatitis C virus‐associated membranoproliferative glomerulonephritis with direct‐acting antiviral therapy after liver transplantation (2019)
  • Author(s): Okamura Keiko、Kuwabara Takashige、Enoki Hiroko、Kohda Yukimasa、Adachi Masataka、Hayashida Shintaro、Inomata Yukihiro、Mukoyama Masashi
  • Journal Title: Nephrology Volume: 24 Pages: 1198～1199
  • DOI: 10.1111/nep.13492
• [Journal Article] Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury (2019)
  • Author(s): Eguchi Koji、Izumi Yuichiro、Nakayama Yushi、Inoue Hideki、Marume Takahiro、Matsuo Naomi、Hiramatsu Akiko、Ono Makoto、Kakizoe Yutaka、Kuwabara Takashige、Nonoguchi Hiroshi、Mukoyama Masashi
  • Journal Title: Nephrology Volume: 24 Pages: 1131～1141
  • DOI: 10.1111/nep.13553
• [Presentation] Intraglomerular crosstalk between mesangial cells and podocytes inhibits normal ER-associated degradation processes and induces podocyte injury in diabetes. (2019)
  • Author(s): Daisuke Fujimoto, Takashige Kuwabara, Yusuke Hata, Shuro Umemoto, Tomoko Kanki, Yoshihiko Nishiguchi, Teruhiko Mizumoto, Manabu Hayata, Yuichiro Izumi, Yutaka Kakizoe, Masashi Mukoyama
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] ABLATION OF MRP8 IN MYELOID CELLS AMELIORATES GLOMERULONEPHRITIS BY AFFECTING MACROPHAGE CHARACTERIZATION (2019)
  • Author(s): Yusuke Hata1, Takashige Kuwabara1, Kiyoshi Mori2, Shuro Umemoto1, Tomoko Kanki1, Daisuke Fujimoto1, Yoshihiko Nishiguchi1, Yutaka kakizoe1, Yuichiro Izumi1, Hideki Yokoi2, Masashi Mukoyama1
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] The predictive role of serum MRP8/14 (S100A8/A9) on mortality in hemodialysis patients (2019)
  • Author(s): Tomoko Kanki, Takashige Kuwabara, Jun Morinaga, Hirotaka Fukami, Shuro Umemoto, Daisuke Fujimoto, Teruhiko Mizumoto, Manabu Hayata, Yutaka Kakizoe, Yuichiro Izumi, Masashi Mukoyama
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] A Case of Ischemic Enteritis Complicated with Chylous Ascites After the Administration of Azelnidipine in a Patient Undergoing Peritoneal Dialysis. (2019)
  • Author(s): Takashige Kuwabara, Makoto Ono, Yu Korogi, Akira Oda, Hideki Inoue, Masashi Mukoyama
  • Organizer: ISPD2019 in Nagoya
  • Int'l Joint Research
• [Presentation] Intraglomerular crosstalk between mesangial cells and podocytes inhibits normal ER-associated degradation processes and induces podocyte injury in diabetic kidney disease. (2019)
  • Author(s): Daisuke Fujimoto, Takashige Kuwabara, Yusuke Hata, Shuro Umemoto, Tomoko Kanki, Yoshihiko Nishiguchi, Teruhiko Mizumoto, Manabu Hayata, Yuichiro Izumi, Yutaka Kakizoe, Masashi Mukoyama
  • Organizer: World Congress of Nephrology
  • Int'l Joint Research
• [Presentation] POTENTIAL ROLE OF MRP8 IN GLOMERULAR INJURY THROUGH INTRAGLOMERULAR CROSSTALK AFFECTING MACROPHAGE CHARACTERIZATION (2019)
  • Author(s): Yusuke Hata1, Takashige Kuwabara1, Kiyoshi Mori2, Shuro Umemoto1, Tomoko Kanki1, Daisuke Fujimoto1, Yoshihiko Nishiguchi1, Hideki Yokoi3, Masashi Mukoyama1
  • Organizer: World Congress of Nephrology
  • Int'l Joint Research
• [Remarks] 熊本大学腎臓内科
  • URL: http://www.kumadai-nephrology.com/