The role of mitochondria in the pathogenesis of low birth weight-related nephropathy

• Project/Area Number: 16K09638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: National Hospital Organization Chiba-East-Hospital
• Principal Investigator: Imasawa Toshiyuki 独立行政法人国立病院機構(千葉東病院臨床研究部), 腎センター, 腎センター長 (80348276)
• Research Collaborator: Yamaguchi Yutaka
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 低出生体重 / 巣状分節性糸球体硬化症 / DoHAD / ミトコンドリア / 糖尿病性腎症 / ミトコンドリア病 / 病理学

Outline of Final Research Achievements

Glomeruli were isolated by the sieving method from kidneys at 4 weeks of age of low birth weight (LBW) rat (N = 5) and normal birth weight ones (n = 5). The isolated glomeruli were cultured and primary culture of glomerular epithelial cells was also performed. Transcriptome analysis of RNA extracted from the obtained glomeruli and primary culture podocytes is outsourced. In the future, we plan to perform epigenetics analysis of the promoter region of the gene which should be expected as candidate genes by the bioinformatics analysis. In addition, by proteome analysis of LBW rat kidney, it was found that mTOR system should be upstream of mitochondrial dysfunction and glycolytic activation in LBW rats. The staining experiments by using antibodies against mTOR pathway revealed that mTOR pathway should be activated in human cases of low-birth related kidney disease.

Academic Significance and Societal Importance of the Research Achievements

日本では2500ｇ未満の「低出生体重」児の割合が約10％とOECD加盟国の中において極めて高い。一方、「将来の健康や特定の病気へのかかりやすさは、胎生期を中心とした極めて初期にその素因が形成される」というDOHaD説を裏付けるように低出生体重個体に於いて腎症の発症や重症化の危険率が高いことを示す報告は枚挙に暇がなく、将来の我が国の疾病構造に現在のこの高い低出生体重率が影響することが懸念されている。未だ検討半ばであるが、低出生体重関連腎症の病態解明を進めることにより、将来起こりえる低出生体重に関連した腎障害に対する対策を行うのに有用であると考える。

Research Products

• [Journal Article] High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy (2017)
  • Author(s): Toshiyuki Imasawa, Emilie Obre, Nad`ege Bellance, Julie Lavie,Tomoko Imasawa,Claire Rigothier, Yahsou Delmas, Christian Combe, Didier Lacombe, Giovanni Benard, St´ephane Claverol, Marc Bonneu, Rodrigue Rossignol
  • Journal Title: FASEB J Volume: 31 Issue: 1 Pages: 294-307
  • DOI: 10.1096/fj.201600293r
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Book] 医学のあゆみ（特集：ポドサイト障害-腎障害における新たな視点） (2018)
  • Author(s): 今澤俊之
  • Total Pages: 5
  • Publisher: 医歯薬出版株式会社
• [Book] 「腎と透析」ベッドサイド検査事典「遺伝学的検査：ミトコンドリア異常症」 (2018)
  • Author(s): 今澤俊之
  • Total Pages: 3
  • Publisher: 東京医学社