Elucidation of the role of homeostatic inflammation in the AKI to CKD transition mechanism focusing on the time phase changes

• Project/Area Number: 17K09704
• 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: Hayata Manabu 熊本大学, 病院, 助教 (30646120)
• Co-Investigator(Kenkyū-buntansha): 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): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: AKI / CKD / マクロファージ / 急性腎障害 / 慢性腎臓病 / 内科

Outline of Final Research Achievements

We examined the role of MRP8 in each phase of the transition process from CKD to CKD. Eight to nine week-old male MRP8 knockout mice and control mice were subjected to left renal ischemia-reperfusion injury for 30 minutes without right nephrectomy. Macrophages were sorted using FACS analysis 2, 7 and 16 days after kidney injury, and then inflammation- and fibrosis-related molecules were analyzed by real-time PCR. As a result, no difference between groups was observed between the MRP8 knockout mouse and the control mouse.

Academic Significance and Societal Importance of the Research Achievements

急性腎障害患者が慢性腎臓病へ移行する過程で、TLR4に関連する炎症が関与していることは示唆されるものの、TLR4リガンドであるMRP8と腎障害慢性化との間に明確な関連を見出す結果には至らなかった。

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 Issue: 1 Pages: 3056-3056
  • DOI: 10.1038/s41598-020-59970-9
  • NAID: 120006956435
  • Peer Reviewed / Open Access
• [Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study (2019)
  • Author(s): Morinaga J, Kakuma T, Fukami H, Hayata M, Uchimura K, Mizumoto T, Kakizoe Y, Miyoshi T, Shiraishi N, Adachi M, Izumi Y, Kuwabara T, Okadome Y, Sato M, Horiguchi H, Sugizaki T, Kadomatsu T, Miyata K, Tajiri S, Tajiri T, Tomita K, Kitamura K, Oike Y, Mukoyama M.
  • Journal Title: Nephrology Dialysis Transplantation Volume: 印刷中 Issue: 5 Pages: 854-860
  • DOI: 10.1093/ndt/gfz236
  • Peer Reviewed / Open Access
• [Journal Article] Refractory peritonitis by spontaneous perforation of the common bile duct in a patient receiving peritoneal dialysis (2017)
  • Author(s): Manabu Hayata, Junji Yamashita, Kentaro Tokunaga, Masashi Ejima, Katsuyuki Sagishima, Shigeki Nakagawa, Daisuke Hashimoto, Hideo Baba, Kosuke Maruyama, Yu Kohrogi, Teruhiko Mizumoto, Masashi Mukoyama and Hidenobu Kamohara
  • Journal Title: Renal Replacement Therapy Volume: 3: 53 Pages: 1-1
  • Peer Reviewed / Open Access
• [Presentation] CKDにおけるMRP8の化学修飾の探索とその意義の検討 (2018)
  • Author(s): 神吉 智子, 桑原 孝成, 梅本 周朗, 藤本 大介, 水本 輝彦, 早田 学, 中山 憲司, 宮崎 有, 井上 貴博, 小川 修, 向山 政志
  • Organizer: 日本腎臓学会
• [Presentation] 糸球体内クロストークにおけるメサンギウム細胞由来因子によるポドサイトERストレス応答の検討 (2018)
  • Author(s): 藤本 大介, 桑原 孝成, 梅本 周朗, 神吉 智子, 水本 輝彦, 早田 学, 泉 裕一郎, 柿添 豊, 向山 政志
  • Organizer: 日本腎臓学会
• [Presentation] 当院で実施した心停止後症候群に対する体温管理療法 (2017)
  • Author(s): 早田学、中原智史、徳永健太郎、江嶋正志、成松紀子、鷺島克之、蒲原英伸
  • Organizer: 第20回日本脳低温療法・体温管理学会
• [Presentation] 抗酒薬シアナマイドによる汎血球減少から壊死性筋膜炎および敗血症性ショックを来した一例 (2017)
  • Author(s): 早田学、徳永健太郎、江嶋正志、鷺島克之、蒲原英伸
  • Organizer: 第1回日本集中治療医学会九州支部学術集会
• [Remarks] 熊本大学病院 腎臓内科
  • URL: http://www.kumadai-nephrology.com/
• [Remarks]
  • URL: http://www.kumadai-nephrology.com/