The role of MALAT1 in the pathogenesis of chronic kidney disease

• Project/Area Number: 15K18987
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: OBANA Masanori 大阪大学, 薬学研究科, 助教 (50745883)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 慢性腎臓病 / 長鎖ncRNA / 長鎖ノンコーディングRNA / 炎症

Outline of Final Research Achievements

Chronic kidney disease (CKD) is a leading cause of kidney failure and cardiovascular diseases. Although there is an unmet medical need for CKD treatments, the mechanisms of physiological and pathological changes of kidney remain to be elucidated. Recently, attention has been drawn to noncoding RNA (ncRNA) as therapeutic targets and biomarkers of diseases. In the present study, we examined the role of MALAT1, long ncRNA, in kidney diseases. The expression of MALAT1 was increased in a mouse model of kidney disease. The kidney injury was suppressed in P2X7R knockout mouse, accompanied by reduced expression of MALAT1. LL37, a ligand of P2X7R, increased MALAT1 expression and induced cell death in cultured podocyte. Our study suggests the possibility that MALAT1, as a downstream signal of LL37/P2X7R, may contribute to cell death in kidney diseases.

Research Products

• [Journal Article] RORγt-expressing cells attenuate cardiac remodeling after myocardial infarction. (2017)
  • Author(s): Enomoto D, Matsumoto K, Yamashita T, Kobayashi A, Maeda M, Nakayama H, Obana M, Fujio Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 8 Pages: e0183584-e0183584
  • DOI: 10.1371/journal.pone.0183584
  • Peer Reviewed / Open Access
• [Journal Article] Adult murine cardiomyocytes exhibit regenerative activity with cell cycle reentry through STAT3 in the healing process of myocarditis. (2017)
  • Author(s): Miyawaki A, Obana M, Mitsuhara Y, Orimoto A, Nakayasu Y, Yamashita T, Fukada SI, Maeda M, Nakayama H, Fujio Y.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 1407-1407
  • DOI: 10.1038/s41598-017-01426-8
  • Peer Reviewed / Open Access
• [Journal Article] Moesin is activated in cardiomyocytes in experimental autoimmune myocarditis and mediates cytoskeletal reorganization with protrusion formation (2016)
  • Author(s): Akimitsu Miyawaki, Yusuke Mitsuhara, Aya Orimoto, Yusuke Nakayasu, Shin-ichi Tsunoda, Masanori Obana, Makiko Maeda, Hiroyuki Nakayama, Yasuo Yoshioka, Yasuo Tsutsumi, Yasushi Fujio
  • Journal Title: The American Journal of Physiology-Heart and Circulatory Physiology Volume: 311 Issue: 2 Pages: 476-486
  • DOI: 10.1152/ajpheart.00180.2016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 腎線維化病態における転写因子OASISの役割 (2017)
  • Author(s): 守沖瞳、尾花理徳、山本彩葉、金本聡自、前田真貴子、今泉和則、中山博之、藤尾慈
  • Organizer: 第132回 日本薬理学会近畿部会