Molecular mechanisms of promotion or suppression in renal tubular interstitial fibrosis

• Project/Area Number: 21590444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Wakayama Medical University
• Principal Investigator: MURAGAKI Yasuteru 和歌山県立医科大学, 医学部, 教授 (40190904)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 疾患モデル動物 / 線維化 / 上皮間葉転換 / TGF-β / 腎尿細管 / TGF-βシグナル / EMT / TRPS1 / Smad3 / 腎 / Trps1 / Arkadia / Smad7 / Trpsl

Research Abstract

Mutations in TRPS1 cause tricho-rhino-pharyngeal syndrome. Trps1 is essential for nephron development, acting downstream of Bmp7. Because Bmp7 counteracts epithelial-to-mesenchymal transition(EMT) and reverses chronic renal injury, we examined the function of Trps1 in renal fibrosis. The results of the experiment suggest that Trps1 deficiency enhances TGF-b1-induced EMT and tubulointestinal fibrosis by modulating the amount of Smad7 through Arkadia/ubiquitin-mediated degradation.

Research Products

• [Journal Article] The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-β-Induced Epithelial-Mesenchymal Transition (2012)
  • Author(s): Ting Gui, Yujing Sun, Aiko Shimokado, Yasuteru Muragaki
  • Journal Title: Journal of signal transduction Volume: 2012 Pages: 1-10
  • DOI: 10.1155/2012/289243
  • Peer Reviewed
• [Journal Article] Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing (2011)
  • Author(s): Kawakatsu M, Kanno S, Gui T, Gai Z, Itoh S, Tanishima H, Oikawa K, Muragaki Y
  • Journal Title: Exp Mol Pathol Volume: 90(1) Pages: 107-15
  • Peer Reviewed
• [Journal Article] Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice (2011)
  • Author(s): Kanno S, Gui T, Itoh S, Gai Z, Sun Y, Oikawa K, Yoshida M, Muragaki Y
  • Journal Title: Exp Mol Pathol Volume: 90(2) Pages: 143-8
  • Peer Reviewed
• [Journal Article] The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles (2011)
  • Author(s): Gai Z, Gui T, Muragaki Y
  • Journal Title: Histol Histopathol Volume: 26(7) Pages: 915-21
  • Peer Reviewed
• [Journal Article] Increased type I and V collagen expression in uterine leiomyomas during the menstrual cycle (2011)
  • Author(s): Iwahashi M, Muragaki Y
  • Journal Title: Fertil Steril Volume: 95(6) Pages: 2137-9
  • Peer Reviewed
• [Journal Article] SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line(BxPC3) and promotes distant metastasis and invasiveness in vivo (2010)
  • Author(s): Ryohei Nishioka, Shunji Itoh, Ting Gui, Zhibo Gai, Kosuke Oikawa, Manabu Kawai, Masaji Tani, Hiroki Yamaue, and Yasuteru Muragaki
  • Journal Title: Exp. Mol. Pathol Volume: 89 Pages: 149-157
  • Peer Reviewed
• [Journal Article] Trps1 haploinsufficiency promotes renal fibrosis by increasing Arkadia expression (2010)
  • Author(s): Zhibo Gai, Gengyin Zhou, Ting Gui, Shunji Itoh, Kosuke Oikawa, Kohsaku Uetani, and Yasuteru Muragaki
  • Journal Title: J. Am. Soc. Nephrol Volume: 21 Pages: 1468-1476
  • Peer Reviewed
• [Journal Article] Trpsl haploinsufficiency promotes renal fibrosis by increasing Arkadia expression. (2010)
  • Author(s): Gai Z, Zhou G, Gui T, Itoh S, Oikawa K, Uetani K, Maregaki Y
  • Journal Title: Journal of the American Society of Nephrology Volume: 21 Pages: 1468-1476
  • Peer Reviewed
• [Journal Article] SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. (2010)
  • Author(s): Nishioka R, Itoh S, Gui T, Gai Z, Oikawa K, Kawai M, Tani M, Yamaue H, Muragaki Y.
  • Journal Title: Experimental Molecular Pathology. Volume: 89 Pages: 149-157
  • Peer Reviewed
• [Journal Article] Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing. (2010)
  • Author(s): Kawakatsu M, Kanno S, Gui T, Gai Z, Itoh S, Tanishima H, Oikawa K, Muragaki Y
  • Journal Title: Experimental Molecular Pathology Volume: 34 Pages: 107-115
  • Peer Reviewed
• [Journal Article] Trps1 functions downstream of Bmp7 in kidney development (2009)
  • Author(s): Gai Z, Zhou G, Itoh S, Morimoto Y, Tanishima H, Hatamura I, Uetani K, Ito M, Muragaki Y
  • Journal Title: J Am Soc Nephrol Volume: 20(11) Pages: 2403-11
  • Peer Reviewed
• [Journal Article] Trps1 Functions Downstream of Bmp7 in Kidney Development (2009)
  • Author(s): Gai Z, Zhou G, Itoh S, Morimoto Y, Hatamura I, Uetani K, Ito M, Muragaki Y
  • Journal Title: Journal of the American Society of Nephrology 20 Pages: 2403-2411
  • Peer Reviewed
• [Journal Article] Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats (2009)
  • Author(s): Okada T, Sakaguchi T, Hatamura I, Saji F, Negi S, Otani H, Muragaki Y, Kawachi H, Shigematsu T.
  • Journal Title: Clinical Experimental Nephrology 13 Pages: 438-446
  • NAID: 10027226471
  • Peer Reviewed
• [Journal Article] Occurrence of central polydactyly, syndactyly, and cleft hand in a single family : report of five hands in three cases (2009)
  • Author(s): Satake H, Ogino T, Takahara M, Kikuchi N, Muramatsu I, Muragaki Y, Kano H.
  • Journal Title: J Hand Surg Am. 34 Pages: 1700-17003
  • Peer Reviewed
• [Presentation] MicroRNAs induced by high concentration of phosphate and calcium are involved in vascular smooth muscle cell calcification (2011)
  • Author(s): Gui Ting
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2011-11-12
• [Presentation] コヒーシン関連タンパクWap1の新規分子機能の検討 (2011)
  • Author(s): 及川恒輔
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-03
• [Presentation] カルシウム輸送体をターゲットにするマイクロRNAはリンで誘導される血管平滑筋細胞の石灰化に関与している (2011)
  • Author(s): 桂ティン
  • Organizer: 第43回日本結合組織学会学術大会
  • Place of Presentation: 別府市
  • Year and Date: 2011-06-11
• [Presentation] Vascular calcification is suppressed by the inhibition of microRNAs targeting calcium channels (2011)
  • Author(s): 桂ティン
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2011-04-29
• [Presentation] Gdf5/Trps1 signaling regulates Prg4 expression in the superficial cells of the articular cartilage (2011)
  • Author(s): Shunji Itoh, Yujing Sun, Ting Gui, Aiko Shimokado, Motohisa Kawakatsu, Kosuke Oikawa, Takashi Ozaki, and Yasuteru Muragaki
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] カルシウム輸送体をターゲットにするマイクロRNAはリンで誘導される血管平滑筋細胞の石灰化に関与している (2011)
  • Author(s): 桂〓、孫玉静、伊藤俊治、及川恒輔、村垣泰光
  • Organizer: 第43回日本結合組織学会学術大会
  • Place of Presentation: 別府
• [Presentation] Vascular calcification is suppressed by the inhibition of microRNAs targeting calcium channels (2011)
  • Author(s): 桂〓、伊藤俊治、及川恒輔、村垣泰光
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
• [Presentation] MicroRNAs induced by high concentration of phosphate and calcium are involved in vascular smooth muscle cell calcification (2011)
  • Author(s): Gui T, Sun Y, Shimokado A, Itoh S, Oikawa K, Muragaki Y
  • Organizer: American Society of Nephrology
  • Place of Presentation: Philadelphia USA
• [Presentation] Renal interstitial fibrosis is promoted through an elevated amount of Arkadia in heterozygous loss of Trpsl. (2010)
  • Author(s): Gai Z, Gui T, Itoh S, Oikawa K, Uetani K, Muragaki Y.
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-06-16
• [Presentation] Gdf5/Trps1は関節形成軟骨細胞の分化を調節する (2010)
  • Author(s): 伊藤俊治、谷島裕之、蓋志博、桂〓、神埜聖治、川勝基久、及川恒輔、村垣泰光
  • Organizer: 日本分子生物学会年会日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] The PRG4 variants associated with sarcoma development have a potential to be therapeutic targets (2010)
  • Author(s): Kosuke Oikawa, Takayuki Hiroi, Shunji Itoh, Ting Gui, Zhibo Gai, Masakatsu Takanashi, Masahiko Kuroda, Yasuteru Muragaki
  • Organizer: 日本分子生物学会年会日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Renal interstitial fibrosis is promoted through an elevated amount of Arkadia in heterozygous loss of Trps1 (2010)
  • Author(s): Zhibo Gai, Gui Ting, Shunji Itoh, Kosuke Oikawa, Kohsaku uetani, Yasuteru Muragaki
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
• [Presentation] 腎尿細管間質線維化における間質細胞の機能と役割 (2009)
  • Author(s): 村垣泰光
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-05-02
• [Presentation] Trps1 is required for the mesenchymal-epit helial transition and ureteral bud branching (2009)
  • Author(s): 盖志博、伊藤俊治、谷島裕之、上谷光作、伊藤正孝、村垣泰光
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Functions of Gdf5 and Trps1 in phalangeal joint formation (2009)
  • Author(s): 伊藤俊治、毛利泰輔、山下友佑、盖志博、神埜聖治、及川恒輔、上谷光作、村垣泰光
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 腎尿細管間質線維化における間質細胞の機能と役割 (2009)
  • Author(s): 村垣泰光
  • Organizer: 第98回日本病理学会総会ワークショップ
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/dept/igakubu/160417/index.html