Kidney regeneration by activating stem cell

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590881
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: HISHKAWA Keiichi The University of Tokyo, The University of TokyoHospital, Associate Professor (50255460)
• Project Period (FY): 2006 – 2007
• Keywords: stem cell / regenerative medicine / renal failure

Research Abstract

Bone morphogenic protein (BMP)-7 is expressed in the adult kidney and reverses chronic renal injury when given exogenously. Here, we report that a histone deacetylase inhibitor, trichostatin A (TSA), attenuates chronic renal injury by augmenting the expression of BMP-7 in kidney side population(SP) cells. We induced accelerated nephrotoxic serum nephritis (NTN) in C57BL/6 mice, and treated them with TSA for 3 weeks. Compared with vehicle-treated NTN mice, treatment with TSA prevented the progression of proteinuria, glomerulosclerosis, interstitial fibrosis and loss of kidney SP cells. Basal gene expression of renoprotective factors such as BMP-7, vascular endothelial growth factor and hepatocyte growth factor was significantly higher in kidney SP cells as compared to non-SP cells. Treatment with TSA significantly up-regulated the expression of BMP-7 only in SP cells but not in non-SP cells. Moreover, initiation of treatment with TSA after 3 weeks of NTN (for 3 weeks, until 6 weeks) partially but significantly reversed renal dysfunction. Our results indicate an important role of SP cells in the kidney as generator cells of BMP-7, and TSA as a stimulator of the cells in reversing chronic renal disease.

Research Products

• [Journal Article] Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury. (2007)
  • Author(s): Imai, N., Hishikawa, K., Marumo, T., Hirahashi, J., Inowa, T., Matsuzaki, Y., Okano, H., ct al.
  • Journal Title: Stem Cells 25 Pages: 2469-2475
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-betal in human renal epithelial cells. (2007)
  • Author(s): Yoshikawa, M., Hishikawa. K., Marumo, T., and Fujita, T.
  • Journal Title: J Am Soc Nephrol 18 Pages: 58-65
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury (2007)
  • Author(s): Imai, N., Hishikawa K., Marumo, T., Hirahashi, J., Inowa, T., Matsuzaki, Y., Okano, H., et. al.
  • Journal Title: Stem Cells 25 Pages: 2469-2475
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells (2007)
  • Author(s): Yoshikawa, M., Hishikawa, K., Marumo, T. & Fujita, T.
  • Journal Title: J Am Soc Nephrol 18 Pages: 58-65
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stem cells and kidney disease (2006)
  • Author(s): Hishikawa, K., and Fujita, T.
  • Journal Title: Hypertens Res 29 Pages: 745-749
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Presentation] Epigenetics制御による腎臓再生のこころみ (2007)
  • Author(s): 菱川慶一
  • Organizer: 第50回日本腎臓学会学術総会
  • Place of Presentation: 浜松
  • Year and Date: 2007-05-26
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Epigenetics and Kidney regeneation (2007)
  • Author(s): Keiichi Hishikawa
  • Organizer: Japanese Society of Nephrology
  • Place of Presentation: Hamamatsu
  • Year and Date: 2007-05-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://kid-endo.umin.jp/a-3-17.html