Study on cell transition in renal tubulointerstitial fibrosis

• Project/Area Number: 24590488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• 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): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腎間質線維化 / 上皮間葉移行 / TGF-β / Klotho / ビタミンD / リン・カルシウム代謝 / 腎尿細管間質線維化 / TGFβ/Smad3 / 尿細管間質線維化 / 片側尿管結紮 / klotho / ビタミンＤ / EMT / MET / TGF-beta / BMP7 / Trps1 / 腎尿細管上皮細胞

Outline of Final Research Achievements

In renal tubulointerstitial fibrosis, tubular epithelial cells are stimulated by various factors and transform from epithelial cells to mesenchymal cells. This epithelial to mesenchymal transition is caused by transforming growth factor (TGF) - beta, which promotes interstitial fibrosis. In this study, we forcused on the relationship between phosphate/calcium metabolism and renal interstitial fibrosis and investigated how a loss of Klotho influenced the degree of fibrosis. As a result, we found that the total loss of Klotho increases the active form of vitamin D, which in turn inhibits TGF-beta signaling, resulting in suppressing tubulointerstitial fibrosis.

Research Products

• [Journal Article] Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression. (2015)
  • Author(s): Sun Y, Nakanishi M, Sato F, Oikawa K, Muragaki Y, Zhou G.
  • Journal Title: BBRC Volume: 456 Issue: 3 Pages: 721-726
  • DOI: 10.1016/j.bbrc.2014.12.039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Elevated serum 1,25(OH)2-vitamin D3 level attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in kl/kl mice. (2014)
  • Author(s): Sun Y, Zhou G, Gui T, Shimokado A, Nakanishi M, Oikawa K, Sato F, Muragaki Y.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 6563-6563
  • DOI: 10.1038/srep06563
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Smad3 plays an inhibitory role in phosphate-induced vascular smooth muscle cell calcification. (2014)
  • Author(s): Shimokado A, Sun Y, Nakanishi M, Sato F, Oikawa K, Akasaka T, Muragaki Y.
  • Journal Title: Experimental and Molecular Pathology Volume: 97 Pages: 458-464
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The loss of Trps1 suppresses ureteric bud branching because of the activation of TGF-βsignaling (2013)
  • Author(s): Gui T, Gai Z, Sun Y, Shimokado A, Muragaki Y, Zhou G
  • Journal Title: Ｄｅｖｅｌｏｐｍｅｎｔａｌ Ｂｉｏｌｏｇｙ Volume: ３７７ Issue: 2 Pages: 415-427
  • DOI: 10.1016/j.ydbio.2013.03.014
  • Peer Reviewed
• [Journal Article] Uterine damage in swine following uterine artery embolization: comparison among gelatin sponge particles and two concentrations of N-butyl cyanoacrylate. (2013)
  • Author(s): Sonomura T, Kawai N, Ikoma A, Minamiguchi H, Ozaki T, Kishi K, Sanda H, Nakata K, Nakai M, Muragaki Y, Sato M.
  • Journal Title: Japanese journal of Radiology Volume: 31(10) Issue: 10 Pages: 685-692
  • DOI: 10.1007/s11604-013-0236-2
  • NAID: 50008985890
  • Peer Reviewed
• [Journal Article] The Role of Tricho-Rhino-Phalangeal Syndrome (TRPS) 1 in Apoptosis during Embryonic Development and Tumor Progression. (2013)
  • Author(s): Sun Y, Gui T, Shimokado A, Muragaki Y
  • Journal Title: Cells Volume: 2(3) Issue: 3 Pages: 496-505
  • DOI: 10.3390/cells2030496
  • Peer Reviewed
• [Journal Article] MicroRNAs that target Ca2+ transporters are involved in vascular smooth muscle cell calcification (2012)
  • Author(s): T. Gui, G. Zhou, Y. Sun, A. Shimokado, S. Itoh, K. Oikawa, Y. Muragaki
  • Journal Title: Lab. Invest Volume: 92 Issue: 9 Pages: 1250-1259
  • DOI: 10.1038/labinvest.2012.85
  • Peer Reviewed
• [Journal Article] Diverse role of macrophages in atheroscrelosis: from inflammatory biology to biomarkerdiscovery (2012)
  • Author(s): Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y
  • Journal Title: Mediators Inflamm Volume: 2012 Pages: 1-14
  • DOI: 10.1155/2012/693083
  • Peer Reviewed
• [Presentation] 1．An Increased Level of Serum 1,25(OH)[sub]2[/sub]-Vitamin D3 Alleviates Renal Tubulointerstitial Fibrosis Induced By Unilateral Ureteral Obstruction in Homozygous Klotho Mutant Mice. (2015)
  • Author(s): Muragaki Y
  • Organizer: USCAP 2015
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-21 – 2015-03-27
• [Presentation] Ureteric bud branching is suppressed by the loss of Trps1 due to the activation of TGF-beta signaling. (2013)
  • Author(s): Gui T, Muragaki Y, Zhou G
  • Organizer: ASN Kidney Week 2013
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] MicroRNAs are involved in phosphate and calcium-induced vascular smooth muscle cell calcification. (2012)
  • Author(s): 桂ティン、孫玉静、下角あい子、伊藤俊治、及川恒輔、尾崎敬、村垣泰光
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京