Identification of microRNAs and their target genes involved in thrombocytopenia associated with disseminated intravascular coagulation

• Project/Area Number: 22K09198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kansai Medical University
• Principal Investigator: KAGEYAMA Kyoko 関西医科大学, 医学部, 研究医員 (80347468)
• Co-Investigator(Kenkyū-buntansha): 竹下 淳 関西医科大学, 医学部, 研究医員 (40433263) ; 中嶋 康文 近畿大学, 医学部, 教授 (70326239)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Project Status: Completed (Fiscal Year 2024)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝子治療 / microRNA / Pyroptosis

Outline of Research at the Start

（臨床研究）感染症とSOFAスコア２点以上上昇のある敗血症患者で、急性期DICスコアの血小板数１点以上の血小板数減少群、０点の血小板数維持群、非敗血症患者群との3群比較で、血小板内miRNA発現の差異を検出する。同時にmRNAの発現解析を施行することで、パスウェイ解析ソフトウェア を用いてmiRNA-mRNAの相互作用を解析し、血小板減少の要因となる遺伝子、蛋白質を予測する。
（細胞実験）血小板系培養細胞（Meg-01）細胞を用いて臨床研究から推定された血小板数減少に関連するmiRNA、ｍRNA、タンパク質を同定する。

Outline of Final Research Achievements

RNA was extracted from platelets of non-septic, septic non-thrombocytopenic, and septic thrombocytopenic groups and analyzed by RNA-seq. IPA revealed marked activation of pyroptosis and inflammasome pathways in the thrombocytopenic group. STRING analysis identified hub genes, whose increased expression (e.g., TNF, NLRP3, Caspase-1) was confirmed by PCR, Western blotting, and ELISA. Related miRNAs were significantly decreased in the thrombocytopenic group, and inhibition of these miRNAs in megakaryocytic cells led to upregulation of target genes.

Academic Significance and Societal Importance of the Research Achievements

１つのmiRNAが、複数の遺伝子の発現に関与していることから、今まで１つのタンパク質の発現変化で説明が出来なかったCommon Diseaseの病態解明、バイオマーカー、治療薬としてmiRNAの解析は期待できる。本研究では、敗血症病態における血小板のmiRNAの役割解明が期待される。

Research Products

• [Journal Article] Comparison of Postoperative Nausea and Vomiting Between Sedation with Remimazolam and Dexmedetomidine in Transcatheter Aortic Valve Replacement Patients: A Single-Center Retrospective Observational Study (2025)
  • Author(s): Mino T, Kitaura A, Sakamoto H, Yoshino Y, Tsukimoto S, Yuasa H, Nakajima Y.
  • Journal Title: J Clin Med . Volume: 14 Issue: 5 Pages: 1759-1759
  • DOI: 10.3390/jcm14051759
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the Adequacy of Using the Supraglottic Airway Device in Cases With Epiglottic Masses: A Mannequin Simulation Study (2025)
  • Author(s): Matsumoto T, Iwamoto T, Nakajima Y, Houri K, Tsujimoto T, Sakamoto H, Kitaura A, Nakayama Y
  • Journal Title: Cureus Volume: 16
  • DOI: 10.7759/cureus.74734
  • Peer Reviewed / Open Access
• [Journal Article] Comparative Analysis of the Hemodynamic Effects of Remimazolam and Propofol During General Anesthesia: A Retrospective Study (2024)
  • Author(s): Tsukimoto S, Kitaura A, Yamamoto R, Hirase C, Nakao S, Nakajima Y, Sanuki T.
  • Journal Title: Cureus Volume: 16
  • DOI: 10.7759/cureus.58340
  • Peer Reviewed / Open Access
• [Presentation] 最近の研究から見えてきた新しいDICの世界 (2024)
  • Author(s): 中嶋康文
  • Organizer: 日本集中治療医学会
  • Invited