Functional analysis of exosomes and RNA binding porteins in inflammatory bowel disease

• Project/Area Number: 17K15911
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Ando Katsuyoshi 旭川医科大学, 大学病院, 助教 (70548677)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: エクソソーム / RNA結合蛋白 / 炎症性腸疾患 / 腸管外合併症 / 実験腸炎モデル / 消化器内科

Outline of Final Research Achievements

We analyzed the mechanism that intestinal and extraintestinal inflammation in inflammatory bowel disease (IBD) developed and exacerbated in regard to exosomes and RNA binding proteins (RBPs). In the experimental colitis models and patients with IBD, specific RBPs involving exosomes derived from serum decreased in active state of colitis. The exacerbation of histological inflammation and elevation of proinflammatory cytokines were determined when administering serum derived from active IBD to the experimental colitis mice. Additionally, the profiles about elevation of proinflammatory cytokines differed from serums between ulcerative colitis and crohn’s disease. Further investigations need to be performed to elucidate the factors derived from serum in IBD, including exosomes, RBPs and targeted RNA, which are possible to exacerbate intestinal and extraintestinal inflammation.

Academic Significance and Societal Importance of the Research Achievements

腸管を主体とした全身の慢性炎症性疾患であり、原因不明で根治治療がない炎症性腸疾患の発生・進展のメカニズムについて、エクソソームやRNA結合蛋白といった新たな側面から解析を行った研究である。これらの成果より、免疫担当細胞やサイトカインではなく、エクソソーム・RNA結合蛋白と標的RNAといった側面から炎症性腸疾患の発症・進展機構を解明し、新規のバイオマーカー・新規治療の開発、および種々の臓器や炎症性疾患におけるエクソソームとRNA結合蛋白の役割を解明していくという新たな研究領域の創生に寄与する。

Research Products

• [Journal Article] A tumor-specific modulation of heterogeneous ribonucleoprotein A0 promotes excessive mitosis and growth in colorectal cancer cells. (2020)
  • Author(s): Konishi H, Fujiya M, Kashima S, Sakatani A, Dokoshi T, Ando K, Ueno N, Iwama T, Moriichi K, Tanaka H, Okumura T
  • Journal Title: Cell Death & Disease Volume: 11 Issue: 4 Pages: 245-245
  • DOI: 10.1038/s41419-020-2439-7
  • Peer Reviewed / Open Access
• [Journal Article] Long-Chain Polyphosphate Is a Potential Agent for Inducing Mucosal Healing of the Colon in Ulcerative Colitis. (2020)
  • Author(s): Fujiya M, Ueno N, Kashima S, Tanaka K, Sakatani A, Ando K, Moriichi K, Konishi H, Kamiyama N, Tasaki Y, Omura T, Matsubara K, Taruishi M, Okumura T.
  • Journal Title: Clinical Pharmacology & Therapeutics Volume: 107 Issue: 2 Pages: 452-461
  • DOI: 10.1002/cpt.1628
  • Peer Reviewed
• [Journal Article] Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient. (2019)
  • Author(s): Kashima S, Tanabe H, Tanino M, Kobayashi Y, Murakami Y, Iwama T, Sasaki T, Kunogi T, Takahashi K, Ando K, Ueno N, Moriichi K, Fukudo M, Tasaki Y, Hosokawa M, Mizukami Y, Fujiya M, Okumura T.
  • Journal Title: Front Oncol. Volume: 9 Pages: 1375-1375
  • DOI: 10.3389/fonc.2019.01375
  • Peer Reviewed / Open Access
• [Journal Article] Gastric submucosa-invasive carcinoma associated with Epstein-Barr virus and endoscopic submucosal dissection: A case report. (2019)
  • Author(s): Kobayashi Y, Kunogi T, Tanabe H, Murakami Y, Iwama T, Sasaki T, Takahashi K, Ando K, Nomura Y, Ueno N, Kashima S, Moriichi K, Takei H, Fujiya M, Okumura T.
  • Journal Title: World J Gastrointest Oncol. Volume: 11 Issue: 10 Pages: 925-932
  • DOI: 10.4251/wjgo.v11.i10.925
  • Peer Reviewed
• [Journal Article] hite coat status is a predictive marker for post-esophageal endoscopic submucosal dissection stricture: a retrospective study. (2019)
  • Author(s): Takahashi K, Fujiya M, Ueno N, Saito T, Sugiyama Y, Murakami Y, Iwama T, Sasaki T, Ijiri M, Tanaka K, Sakatani A, Ando K, Nomura Y, Kashima S, Goto M, Moriichi K, Okumura T.
  • Journal Title: Esophagus. Volume: - Issue: 3 Pages: 258-263
  • DOI: 10.1007/s10388-019-00659-y
  • Peer Reviewed
• [Journal Article] Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms (2019)
  • Author(s): Moriichi K, Fujiya M, Kobayashi Y, Murakami Y, Iwama T, Kunogi T, Sasaki T, Ijiri M, Takahashi K, Tanaka K, Sakatani A, Ando K, Nomura Y, Ueno N, Kashima S, Ikuta K, Tanabe H, Mizukami Y, Saitoh Y, Okumura T.
  • Journal Title: Molecules Volume: 24 Issue: 6 Pages: 1106-1106
  • DOI: 10.3390/molecules24061106
  • Peer Reviewed / Open Access
• [Journal Article] A case of gastric carcinoma with lymphoid stroma diagnosed by an endoscopic ultrasound-guided fine-needle biopsy. (2019)
  • Author(s): Tanabe H, Ando K, Sutoh D, Ohta K, Ohdaira H, Suzuki Y, Fujiya M, Okumura T.
  • Journal Title: J Clin Ultrasound. Volume: 47 Issue: 7 Pages: 419-422
  • DOI: 10.1002/jcu.22696
  • Peer Reviewed
• [Journal Article] Endoscopic Fine-Needle Aspiration Is Useful for the Treatment of Pneumatosis Cystoides Intestinalis With Intussusception. (2019)
  • Author(s): Takahashi K, Fujiya M, Ueno N, Ando K, Kashima S, Moriichi K, Okumura T.
  • Journal Title: Am J Gastroenterol. Volume: 114 Issue: 1 Pages: 13-13
  • DOI: 10.14309/ajg.0000000000000069
  • Peer Reviewed
• [Journal Article] Minute duodenal metastasis in a patient with thoracic esophageal squamous cell carcinoma successfully treated with chemoradiotherapy. (2019)
  • Author(s): Ando K, Fujiya M, Okumura T.
  • Journal Title: Dig Endosc. Volume: 31 Issue: 1 Pages: 102-102
  • DOI: 10.1111/den.13275
  • Peer Reviewed
• [Journal Article] Successful medical treatment for a Crohn's disease patient with a perforation by a second-generation patency capsule. (2018)
  • Author(s): Tanabe H, Ando K, Ohdaira H, Suzuki Y, Konuma I, Ueno N, Fujiya M, Okumura T.
  • Journal Title: Endosc Int Open. Volume: 6 Issue: 12 Pages: E1436-E1438
  • DOI: 10.1055/a-0752-9903
  • Peer Reviewed
• [Journal Article] The Incidence and Risk Factors of Venous Thromboembolism in Patients with Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study (2018)
  • Author(s): Ando Katsuyoshi、Fujiya Mikihiro、Nomura Yoshiki、Inaba Yuhei、Sugiyama Yuya、Kobayashi Yu、Iwama Takuya、Ijiri Masami、Takahashi Keitaro、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Tanabe Hiroki、Mizukami Yusuke、Akasaka Kazumi、Fujii Satoshi、Yamada Satoshi、Nakase Hiroshi、Okumura Toshikatsu
  • Journal Title: Digestion Volume: NA Issue: 4 Pages: 1-9
  • DOI: 10.1159/000495289
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: a retrospective cohort study (2018)
  • Author(s): Ando Katsuyoshi、Fujiya Mikihiro、Nomura Yoshiki、Inaba Yuhei、Sugiyama Yuuya、Iwama Takuya、Ijiri Masami、Takahashi Keitaro、Tanaka Kazuyuki、Sakatani Aki、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Mizukami Yusuke、Okumura Toshikatsu
  • Journal Title: Intestinal Research Volume: 16 Issue: 3 Pages: 416-416
  • DOI: 10.5217/ir.2018.16.3.416
  • Peer Reviewed
• [Journal Article] Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication. (2018)
  • Author(s): Tanabe H, Yoshino K, Ando K, Nomura Y, Ohta K, Satoh K, Ichiishi E, Ishizuka A, Otake T, Kohgo Y, Fujiya M, Okumura T.
  • Journal Title: Ann Clin Microbiol Antimicrob. Volume: 17 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s12941-018-0281-x
  • NAID: 120006541974
  • Peer Reviewed
• [Journal Article] Takayasu’s arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17 (2018)
  • Author(s): Fujiya Mikihiro、Kashima Shin、Sugiyama Yuya、Iwama Takuya、Ijiri Masami、Tanaka Kazuyuki、Takahashi Keitaro、Ando Katuyoshi、Nomura Yoshiki、Ueno Nobuhiro、Goto Takuma、Moriichi Kentaro、Mizukami Yusuke、Okumura Toshikatsu、Sasajima Junpei、Fujishiro Daisuke、Okamoto Kensaku、Makino Yuichi
  • Journal Title: Gut Pathogens Volume: 10 Issue: 1 Pages: 22-22
  • DOI: 10.1186/s13099-018-0251-z
  • Peer Reviewed
• [Journal Article] A Case of Alpha-Fetoprotein-Producing Adenocarcinoma of the Esophagogastric Junction in which Long-Term Survival Was Achieved by Means of Individualized Multidisciplinary Therapy (2018)
  • Author(s): Tanaka Kazuyuki、Fujiya Mikihiro、Ijiri Masami、Takahashi Keitaro、Ando Katsuyoshi、Nomura Yoshiki、Ueno Nobuhiro、Kashima Shin、Goto Takuma、Sasajima Junpei、Ito Takahiro、Moriichi Kentaro、Mizukami Yusuke、Tanabe Hiroki、Okumura Toshikatsu
  • Journal Title: Journal of Gastrointestinal Cancer Volume: - Issue: 3 Pages: 617-620
  • DOI: 10.1007/s12029-018-0078-3
  • NAID: 120006496820
  • Peer Reviewed
• [Journal Article] The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: A retrospective cohort study (2018)
  • Author(s): Ando K, et al.
  • Journal Title: Intestinal Research Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] IBDに合併する血栓症の現状と対策 (2018)
  • Author(s): 安藤 勝祥、藤谷 幹浩
  • Journal Title: IBD Research Volume: 1 Pages: 48-53
• [Journal Article] Efficacy of Vonoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Multicenter Study and a Review of the Literature (2017)
  • Author(s): Tanabe Hiroki、Ando Katsuyoshi、Sato Kiichi、Ito Takahiro、Goto Mitsuru、Sato Tomonobu、Fujinaga Akihiro、Kawamoto Toru、Utsumi Tatsuya、Yanagawa Nobuyuki、Ichiishi Eiichiro、Otake Takaaki、Kohgo Yutaka、Nomura Yoshiki、Ueno Nobuhiro、Sugano Hiroko、Kashima Shin、Moriichi Kentaro、Fujiya Mikihiro、Okumura Toshikatsu
  • Journal Title: Digestive Diseases and Sciences Volume: 62 Issue: 11 Pages: 3069-3076
  • DOI: 10.1007/s10620-017-4664-1
  • Peer Reviewed
• [Journal Article] Pilot study of endoscopic retrograde 3-dimensional ? computed tomography enteroclysis for the assessment of Crohn’s disease (2017)
  • Author(s): Tanabe Hiroki、Ito Takahiro、Inaba Yuhei、Ando Katsuyoshi、Nomura Yoshiki、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Fujiya Mikihiro、Okumura Toshikatsu
  • Journal Title: European Journal of Radiology Open Volume: 4 Pages: 58-62
  • DOI: 10.1016/j.ejro.2017.04.003
  • NAID: 120006471090
  • Peer Reviewed
• [Presentation] 寛解期潰瘍性大腸炎における通常・拡大内視鏡を用いた活動性評価と再燃予測 (2020)
  • Author(s): 安藤 勝祥、藤谷 幹浩、奥村 利勝
  • Organizer: 第47回日本潰瘍学会総会
• [Presentation] 寛解維持療法中の潰瘍性大腸炎患者における通常・拡大内視鏡観察による活動性のモニタリングと治療適正化に関する検討 (2019)
  • Author(s): 安藤 勝祥、杉山 雄哉、村上 雄紀、岩間 琢哉、久野木 健仁、佐々木 貴弘、高橋 慶太郎、上野 伸展、嘉島 伸、盛一 健太郎、田邊 裕貴、藤谷 幹浩、奥村 利勝
  • Organizer: 第10回日本炎症性腸疾患学会学術集会
• [Presentation] The correlation among the skeletal muscle, visceral fat and clinical course in patients with Crohn’s disease treated with anti-TNF-α antibody (2019)
  • Author(s): Katsuyoshi Ando, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Mikihiro Fujiya, Toshikatsu Okumura
  • Organizer: The 7th Annual Meeting of AOCC
  • Int'l Joint Research
• [Presentation] クローン病に対する生物学的製剤投与時における骨格筋筋肉量・内臓脂肪量と臨床経過 (2019)
  • Author(s): 安藤 勝祥, 藤谷 幹浩, 奥村 利勝
  • Organizer: 第105回日本消化器病学会総会
• [Presentation] 潰瘍性大腸炎における通常観察と拡大内視鏡観察による粘膜治癒の評価と再燃予測 (2019)
  • Author(s): 安藤 勝祥, 藤谷 幹浩, 奥村 利勝
  • Organizer: 第97回日本消化器内視鏡学会総会
• [Presentation] 炎症性腸疾患入院患者における静脈血栓塞栓症の発症頻度 多施設前向き研究 (2019)
  • Author(s): 岩間 琢哉 安藤 勝祥, 稲葉 勇平, 杉山 雄哉, 村上 雄紀, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 山田 聡, 仲瀬 裕志, 藤谷 幹浩, 奥村 利勝
  • Organizer: JDDW2019
• [Presentation] The incidence of venous thromboembolism with inflammatory bowel disease in Japanese inpatients: A prospective cohort study (2018)
  • Author(s): Katsuyoshi Ando, Mikihiro Fujiya, Yoshiki Nomura, Yuhei Inaba, Yu Kobayashi, Yuuki Murakami, Takuya Iwama, Takehito Kunoki, Masami Ijiri, Keitaro Takahashi, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Satoshi Yamada, Hiroshi Nakase, Toshikatsu Okumura.
  • Organizer: 6th Annual meeting of Asian Organization
  • Int'l Joint Research
• [Presentation] 内臓脂肪と腸腰筋筋肉量の変化からみたクローン病術後長期経過の検討 (2018)
  • Author(s): 安藤 勝祥、小林 裕、村上 雄紀、佐藤 裕基、岩間 琢哉、久野木 健仁、高橋 慶太郎、河端 秀賢、林 明宏、上野 伸展、後藤 拓磨、嘉島 伸、笹島 順平、盛一 健太郎、田邊 裕貴、水上 裕輔、藤谷 幹浩、奥村 利勝
  • Organizer: JDDW2018
• [Presentation] 手術前後のサルコペニア・内臓脂肪量の変化とクローン病術後経過に関する検討 (2018)
  • Author(s): 安藤 勝祥、小林 裕、村上 雄紀、岩間 琢哉、佐々木 貴弘、久野木 健仁、高橋 慶太郎、上野 伸展、嘉島 伸、盛一 健太郎、田邊 裕貴、藤谷 幹浩、奥村 利勝
  • Organizer: 第9回日本炎症性腸疾患学会
• [Presentation] 腸炎モデルマウスにおける RNA結合蛋白hnRNP A1の 腸管粘膜修復作用 (2018)
  • Author(s): 安藤 勝祥、藤谷 幹浩 、小西 弘晃 、 上野 伸展、奥村 利勝
  • Organizer: 第55回日本消化器免疫学会
• [Presentation] 小腸障害モデルマウスにおけるRNA結合蛋白hnRNP A1の 粘膜修復作用 (2018)
  • Author(s): 安藤 勝祥、藤谷 幹浩 、奥村 利勝
  • Organizer: 第46回日本潰瘍学会
• [Presentation] The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: A retrospective and prospective study (2017)
  • Author(s): Ando K, et al.
  • Organizer: Advances in Inflammatory Bowel Disease 2017
  • Int'l Joint Research
• [Presentation] The incidence and risk factors of venous thromboembolism in Japanese patients with inflammatory bowel disease. (2017)
  • Author(s): Iwama T, Ando K, et al.
  • Organizer: Asian Organisation of Crohn's and Colitis Annual meeting 5th
  • Int'l Joint Research
• [Presentation] 炎症性腸疾患入院患者における静脈血栓塞栓症の発症頻度とリスク層別化についての検討 (2017)
  • Author(s): 安藤 勝祥、他
  • Organizer: JDDW2017
• [Presentation] 潰瘍性大腸炎におけるUlcerative Colitis Endoscopic Index of Severity(UCEIS)と拡大内視鏡所見を用いた疾患活動性評価と再燃予測に関する検討 (2017)
  • Author(s): 安藤 勝祥、他
  • Organizer: 第103回日本消化器病学会総会
• [Presentation] Efficacy of quantitated autofluorescence imaging endoscopy in patients with ulcerative colitis: A multicenter study (2017)
  • Author(s): Moriichi K, Fujiya M, Sugiyama Y, Iwama T, Ijiri M, Tanaka K, Takahashi K, Ando K, Nomura Y, Ueno N, Kashima S, Inaba Y, Ito T, Okumura T.
  • Organizer: Advances in Inflammatory Bowel Disease 2017