Integrated Analysis of microRNA and mRNA Gene Expression Profiling for Non-syndromic Acute Type A Aortic Dissection

• Project/Area Number: 24791469
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Jichi Medical University
• Principal Investigator: KIMURA NAOYUKI 自治医科大学, 医学部, 講師 (20382898)
• Research Collaborator: NAKAE Susumu 東京大学, 医科学研究所システム疾患モデル研究センター, 准教授 (60450409) ; MATSUMOTO Kenji 国立成育医療研究センター, 研究所免疫アレルギー/感染研究部, 部長 (60181765) ; FUTAMURA Kyoko 国立成育医療研究センター, 研究所免疫アレルギー/感染研究部, 研究員 (60596956) ; FISCHBEIN Michael P. 米国スタンフォード大学, 心臓胸部外科, 講師
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: microRNA / 急性大動脈解離 / 網羅的遺伝子発現解析 / DNAマイクロアレイ / マイクロRNA / 網羅的遺伝子検索 / TGF / アメリカ合衆国

Outline of Final Research Achievements

We performed an integrated gene expression profiling for miRNA and mRNA to identify key molecules driving dissection development. Total RNA including miRNA was isolated from the ascending aorta in patients with acute aortic dissection (AAD) (n=6) and transplant donors (n=5).　Comprehensive gene expression analysis was performed using both mRNA and miRNA microarray. Of up/down-regulated mRNA, mRNAs whose gene-expression was regulated by up/down-regulated miRNAs were estimated bioinformatically. 92 miRNAs (6.7%, 92/1368) and 1,669 genes (3.9%, 1,669/42,545) were up/down-regulated in the AAD group. Of the 1,669 genes, 138 (8.3%, 138/1,669) were regulated by the up/down-regulated miRNAs. Pathway analysis revealed genes involved in TGFβ signaling (TGFB1, BAMBI), MMP (TIMP), and JAK2 (JAK2) were included in the target genes. qRT-PCR confirmed these genes were up/down-regulated in the AAD group. Our results suggested chronic inflammation might be associated with the disease development.

Research Products

• [Journal Article] Gene expression profiling of acute type A aortic dissection combined with in vitro assessment. (2017)
  • Author(s): Kimura N, Futamura K, Arakawa M, Okada N, Emrich F, Okamura H, Sato T, Shudo Y, Koyano TK, Yamaguchi A, Adachi H, Matsuda A, Kawahito K, Matsumoto K, Fischbein MP.
  • Journal Title: European Journal of Cardio-Thoracic Surgery Volume: 52 Issue: 4 Pages: 810-817
  • DOI: 10.1093/ejcts/ezx095
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Gene expression profiling and in vitro human aortic cell experiments for non-syndromic acute type A aortic dissection (2016)
  • Author(s): Kimura N, Futamura K, Arakawa M, Okada N, Emrich F, Okamura H, Sato T, Shudo Y, Koyano TK, Matsuda A, Yamaguchi A, Adachi H, Matsumoto K, Fischbein MP
  • Organizer: 30th European Association for Cardiothoracic Surgery, Annual Meeting
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2016-10-02