Identification of new myeloid-derived fibrosis-inducing cells accounting for cardiorenal connection in diabetic nephropathy

• Project/Area Number: 15K19449
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2016); Kanazawa University (2015)
• Principal Investigator: Sagara Akihiro 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, 研究員 (00707060)
• Co-Investigator(Renkei-kenkyūsha): Wada Takashi 金沢大学, 大学院 腎病態統御学・腎臓内科学, 教授 (40334784)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 骨髄由来細胞 / 繊維化 / 心腎連関 / 線維化

Outline of Final Research Achievements

To chase and identify fibrosis-related cell types, we used unilateral ureteral obstruction model mice, which showed renal and heart fibrosis, in combination with GFP-based tracing systems such as bone-marrow transplantation (BMT). We found BM-derived mononuclear cell cluster of CD45+Sca1+ cells mobilized and accumulated in the fibrotic lesions of kidney and heart using flow cytometry (FCM). The CD45+Sca1+ cells had an activating potential for collagen production of cultured fibroblasts and also produced type 1 collagen by themselves. Genechip analyses and FCM revealed the subpopulation of CD45+Sca1+ cells, which were related to chemotaxis and innate immunity. These cells were also detected in human peripheral blood and increased in proportion to kidney dysfunction. In this study, we succeeded to identify a new myeloid-derived fibrosis-inducing cells, which could provide a new avenue in fibrosis.

Research Products

• [Journal Article] Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction. (2017)
  • Author(s): Oshima M, Iwata Y, Furuichi K, Sakai N, Shimizu M, Hara A, Kitajima S, Toyama T, Shinozaki Y, Sagara A, Umeda E, Kaneko S, Arai S, Miyazaki T, Wada T.
  • Journal Title: Clin Exp Nephrol Volume: 21 Issue: 1 Pages: 35-42
  • DOI: 10.1007/s10157-016-1240-5
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis (2016)
  • Author(s): Kitagawa K, Furuichi K, Sagara A, Shinozaki Y, Kitajima S, Toyama T, Hara A, Iwata Y, Sakai N, Shimizu M, Kaneko S, Wada T②Kitagawa K, Furuichi K, Sagara A, Shinozaki Y, Kitajima S, Toyama T, Hara A, Iwata Y, Sakai N, Shimizu M, Kaneko S, Wada T
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 5 Pages: 703-711
  • DOI: 10.1007/s10157-015-1199-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease. (2015)
  • Author(s): Kitajima S, Iwata Y, Furuichi K, Sagara A, Shinozaki Y, Toyama T, Sakai N, Shimizu M, Sakurai T, Kaneko S, Wada T.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 2 Pages: 218-25
  • DOI: 10.1007/s10157-015-1150-y
  • Peer Reviewed / Open Access
• [Journal Article] Impact of kidney function and urinary protein excretion on intima-media thickness in Japanese patients with type 2 diabetes. (2015)
  • Author(s): Nakade Y, Toyama T, Furuichi K, Kitajima S, Miyajima Y, Fukamachi M, Sagara A, Shinozaki Y, Hara A, Shimizu M, Iwata Y, Oe H, Nagahara M, Horita H, Sakai Y, Kaneko S, Wada T.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 5 Pages: 909-917
  • DOI: 10.1007/s10157-015-1088-0
  • Peer Reviewed / Open Access
• [Journal Article] Relapse and its remission in Japanese patients with idiopathic membranous nephropathy. (2015)
  • Author(s): Kitajima S, Furuichi K, Sakai N, Sagara A, Shinozaki Y, Toyama T, Iwata Y, Shimizu M, Yokoyama H, Kaneko S, Wada T
  • Journal Title: Clinical and Experimental Nephrology Volume: 19 Issue: 2 Pages: 278-283
  • DOI: 10.1007/s10157-014-0987-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Identi cation of Myeloid-Derived Fibrosis-Inducing Cells Presumably Accounting for Cardiorenal Connection in Chronic Kidney Disease (2016)
  • Author(s): Akihiro Sagara, Norihiko Sakai, Yasunori Iwata, Kengo Furuichi, Yasuhiko Yamamoto, Takashi Wada
  • Organizer: ASN Kidney Week 2016
  • Place of Presentation: Chicago
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] 尿細管障害におけるRAGE分子種の機能的役割 (2016)
  • Author(s): 宮川 太郎, 相良 明宏, 篠崎 康之, 北島 信治, 遠山 直志, 原 章規, 岩田 恭宜, 坂井 宣彦, 清水 美保, 古市 賢吾, 山本 靖彦, 和田 隆志
  • Organizer: 第５9回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-19
• [Presentation] 腎線維化機序におけるオートタキシンの意義義 (2016)
  • Author(s): 中村 美貴, 坂井 宣彦，上川 康貴，相 良明宏， 篠崎 康之, 北島 信治, 原 章規, 岩田 恭宜, 清水 美保, 古市 賢吾, 和田 隆志
  • Organizer: 第５9回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-18
• [Presentation] 骨髄由来細胞による心腎連関機序 (2016)
  • Author(s): 相良 明宏, 坂井 宣彦, 岩田 恭宜, 古市 賢吾, 山本 靖彦, 和田 隆志
  • Organizer: 第５9回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] 腎疾患におけるApoptosis inhibitor of macrophage(AIM)発現の意義 (2016)
  • Author(s): 大島 恵，小林 拓, 越野 瑛久, 中川 詩織, 山村 雄太, 相良 明宏, 篠崎 康之, 北島 信治, 原 章規, 岩田 恭宜, 坂井 宣彦, 清水 美保, 古市 賢吾, 和田 隆志
  • Organizer: 第５9回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
• [Presentation] 慢性腎臓病が頸動脈エコー指標であるIMTに与える影響 (2015)
  • Author(s): 中出祐介，遠山直志，北島信治，相良明宏，原章規，岩田恭宜，坂井宣彦，古市賢吾，和田隆志
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-06-05
• [Presentation] 慢性腎臓病における腎ー腸連関の意義 (2015)
  • Author(s): 篠﨑康之，相良明宏，北島信治，岩田恭宜，坂井宣彦，清水美保，古市賢吾，和田隆志
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-06-05