Analysis of novel transcriptional mechanisms and identification of non-coding RNAs contributing renal fibrosis.

• Project/Area Number: 26860627
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: MIMURA IMARI 東京大学, 医学部附属病院, 助教 (00727084)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎線維化 / 非翻訳RNA / 腎尿細管間質 / 線維化 / ヒストン / non-coding RNA / 慢性腎不全 / 低酸素

Outline of Final Research Achievements

The main researcher of this project administered Dznep, which is one of inhibitors of histone repressive mark H3K27me3, to chronic kidney disease model mice in order to identify novel epigenetic mechanisms and factors which contribute to the reduction of tubulointerstitial fibrosis. I used laser captured microdissection to cut out only tubular cells from in vivo mice cortexes. I performed genome-wide analysis of RNA using high throughput sequencers. As a result, I identified changes of genes or lincRNAs expressions which are associated with renal fibrosis. These results suggested that there is a possibility that epigenetic factors driven by Dznep lead to amelioration of tubulointerstitial fibrosis.

Research Products

• [Journal Article] Epigenetic memory in kidney diseases. (2016)
  • Author(s): Mimura I.
  • Journal Title: Kidney International. Volume: 89 Issue: 2 Pages: 274-277
  • DOI: 10.1016/j.kint.2015.12.026
  • Peer Reviewed
• [Journal Article] Epigenetic Changes Induced by Hypoxia-Inducible Factor: a Long Way Still To Go as a Target for Therapy? (2015)
  • Author(s): Nangaku M, Inagi R, Mimura I, Tanaka T.
  • Journal Title: Journal of American Society of Nephrology. Volume: 26 Pages: 1478-1480
  • Peer Reviewed
• [Journal Article] Evolution of epigenetics in kidney diseases. (2015)
  • Author(s): Mimura I.
  • Journal Title: Nihon Jinzo Gakkai Shi. Volume: 57 Pages: 241-247
  • NAID: 40020351548
• [Journal Article] How the Target Hemoglobin of Renal Anemia Should Be (2015)
  • Author(s): Mimura I, Tanaka T, Nangaku M
  • Journal Title: Nephron Volume: 131 Issue: 3 Pages: 202-9
  • DOI: 10.1159/000440849
  • Peer Reviewed
• [Journal Article] Quantitating intracellular oxygen tension in vivo by phosphorescence lifetime measurement (2015)
  • Author(s): Hirakawa Y, Yoshihara T, Kamiya M, Mimura I, Fujikura D, Masuda T, Kikuchi R, Takahashi I, Urano Y, Tobita S, Nangaku M.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 17838-17838
  • DOI: 10.1038/srep17838
  • Peer Reviewed / Open Access
• [Journal Article] Role of Uremic Toxins in Erythropoiesis-Stimulating Agent Resistance in Chronic Kidney Disease and Dialysis Patients. (2015)
  • Author(s): Nangaku M, Mimura I, Yamaguchi J, Higashijima Y, Wada T, Tanaka T.
  • Journal Title: Journal of Renal Nutrition Volume: 25 Issue: 2 Pages: 160-163
  • DOI: 10.1053/j.jrn.2014.10.011
  • Peer Reviewed
• [Journal Article] Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements. (2014)
  • Author(s): Inoue T, Kohro T, Tanaka T, Kanki Y, Li G, Poh HM, Mimura I, Kobayashi M, Taguchi A, Maejima T, Suehiro JI, Sugiyama A, Kaneki K, Aruga H, Dong S, Stevens JF, Yamamoto S, Tsutsumi S, Fujita T, Ruan X, Aburatani H, Nangaku M, Ruan Y, Kodama T, Wada Y.
  • Journal Title: Genome Biology Volume: 15 Issue: 4
  • DOI: 10.1186/gb-2014-15-4-r63
  • Peer Reviewed / Open Access
• [Journal Article] Direct Evidence for Pitavastatin Induced Chromatin Structure Change in the KLF4 Gene in Endothelial Cells. (2014)
  • Author(s): Maejima T, Inoue T, Kanki Y, Kohro T, Li G, Ohta Y, Kimura H, Kobayashi M, Taguchi A, Tsutsumi S, Iwanari H, Yamamoto S, Aruga H, Dong S, Stevens JF, Poh HM, Yamamoto K, Kawamura T, Mimura I,
  • Journal Title: PLoS One. Volume: 9 Issue: 5 Pages: e96005-e96005
  • DOI: 10.1371/journal.pone.0096005
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetics in kidney diseases. (2014)
  • Author(s): Mimura I, Nangaku M
  • Journal Title: Rinsho Byori Volume: 62 Pages: 180-189
  • NAID: 40020017459
• [Journal Article] Endothelin-converting enzyme is a plausible target gene for hypoxia-inducible factor. (2014)
  • Author(s): Khamaisi M, Toukan H, Axelrod JH, Rosenberger C, Skarzinski G, Shina A, Meidan R, Koesters R, Rosen S, Walkinshaw G, Mimura I, Nangaku M, Heyman SN.
  • Journal Title: Kidney International Volume: 87 Issue: 4 Pages: 761-770
  • DOI: 10.1038/ki.2014.362
  • Peer Reviewed
• [Journal Article] Hypoxia and fibrosis in chronic kidney disease: crossing at pericytes. (2014)
  • Author(s): Kawakami T, Mimura I, Shoji K, Tanaka T, Nangaku M
  • Journal Title: Kidney International Suppl Volume: 4 Pages: 107-112
  • Peer Reviewed / Open Access
• [Presentation] 腎臓領域におけるエピジェネティクスの進展 (2016)
  • Author(s): 三村 維真理
  • Organizer: 第17回神田川腎セミナー
  • Place of Presentation: 経団連会館（東京都千代田区）
  • Year and Date: 2016-01-29
  • Invited
• [Presentation] Identification of novel microRNAs inhibiting tubulointerstitial fibrosis. (2015)
  • Author(s): 三村 維真理
  • Organizer: Kidney Summit
  • Place of Presentation: 第一ホテル東京（東京都港区）
  • Year and Date: 2015-12-20
• [Presentation] りん光寿命測定を用いた腎臓尿細管細胞内酸素分圧の測定 (2015)
  • Author(s): 平川陽亮、三村維真理、吉原利忠、神谷真子、浦野泰照、飛田成史、南学正臣
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-04
• [Presentation] 低酸素とTGF-βは、下流にあるIGFBP3を介して、尿細管上皮細胞にapoptosisを誘導する (2015)
  • Author(s): 串田夏樹、野村征太郎、藤田隆教、三村維真理、南学正臣、油谷浩幸
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Quantitating intracellular oxygen tension in kidney by phosphorescence lifetime measurement. (2015)
  • Author(s): Yosuke, Hirakawa, Imari, Mimura, Toshitada, Yoshihara, Mako, Kamiya, Yasuteru, Urano, Seiji, Tobita, Masaomi, Nangaku
  • Organizer: American Society of Nephrology
  • Place of Presentation: SanDiego（アメリカ合衆国）
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Estimation of intracellular oxygen concentration in diabetic kidney by phosphorescence lifetime measurement (2015)
  • Author(s): Yosuke, Hirakawa, Imari, Mimura, Toshitada, Yoshihara, Mako, Kamiya, Yasuteru, Urano, Seiji, Tobita, Masaomi, Nangaku
  • Organizer: Keystone Symposia 2015
  • Place of Presentation: ウェスティン都ホテル京都（京都府京都市）
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] りん光寿命測定を用いた生体内での尿細管細胞内低酸素の検出 (2015)
  • Author(s): 平川陽亮、三村維真理、吉原利忠、神谷真子、浦野泰照、飛田成史、南学正臣
  • Organizer: 第6回分子腎臓フォーラム
  • Place of Presentation: グランフロント大阪（大阪府大阪市）
  • Year and Date: 2015-09-05
• [Presentation] Detection and quantification of intracellular hypoxia of kidney by phosphorescence lifetime measurement using BTPDM1. (2015)
  • Author(s): 平川陽亮、三村維真理、吉原利忠、神谷真子、浦野泰照、飛田成史、南学正臣
  • Organizer: 第3回低酸素研究会
  • Place of Presentation: 早稲田大学先端生命医科学センター（東京都新宿区）
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] りん光寿命測定を用いた腎の低酸素の検出と定量化 (2015)
  • Author(s): 平川陽亮、三村維真理、吉原利忠、神谷真子、浦野泰照、飛田成史、南学正臣
  • Organizer: 第58回日本腎臓学会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 慢性腎臓病の進展とエピゲノム~低酸素刺激によるクロマチン立体構造変化 (2014)
  • Author(s): 三村 維真理
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25
  • Invited
• [Presentation] エピジェネティクスからみた慢性腎臓病―病態の解明と新規治療法に向けて (2014)
  • Author(s): 三村 維真理
  • Organizer: 第57回日本腎臓学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-05
  • Invited
• [Book] Biomarkers in Diseases.: Methods, Discoveries and Applications. Biomarkers in Kidney Disease. (2015)
  • Author(s): Imari Mimura, Masaomi Nangaku
  • Total Pages: 21
  • Publisher: Springer
• [Book] 日本腎臓学会雑誌 (2015)
  • Author(s): 三村 維真理
  • Total Pages: 7
  • Publisher: 日本腎臓学会
• [Book] 医学のあゆみ (2014)
  • Author(s): 三村 維真理、田中 哲洋
  • Total Pages: 6
  • Publisher: 医歯薬出版