Analysis of pathogenesis of Nakajo-Nishimura syndrome associated with proteasome-dysfunction by using disease-specific iPS cell.

• Project/Area Number: 24790997
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Yokohama City University
• Principal Investigator: YANAGIMACHI Masakatsu 横浜市立大学, 医学部, 助教 (00608911)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 中條-西村症候群 / 自己炎症性疾患 / プロテオソーム / iPS細胞 / 中條西村症候群 / Proteasome / 疾患iPS細胞研究 / 中條―西村症候群

Outline of Final Research Achievements

Nakajo-Nishimura syndrome (NNS) is a proteasome-associated autoinflammatory syndrome caused by PSMB8 gene mutation. The pathogenesis of and treatment for NNS remain to be established. We have studied these by using NNS-specific iPS cell.
Chymotrypsin-like proteasome activity decreased in monocyte-like cells derived from NNS-specific iPS cells compared to that from control iPS cells. Inflammatory cytokines such as IL-6 were higher in culture supernatant of monocyte-like cells derived from NNS-specific iPS cells than that from control iPS cells. These results were consistent with those of primary monocyte of NNS patients. We are going to continue the study for pathogenesis of and drug discovery for NNS with this technique.

Research Products

• [Journal Article] Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell-free conditions. (2013)
  • Author(s): Yanagimachi MD, Niwa A, Tanaka T, Honda-Ozaki F, Nishimoto S, Murata Y, Yasumi T, Ito J, Tomida S, Oshima K, Asaka I, Goto H, Heike T, Nakahata T, Saito MK.
  • Journal Title: PLoS One Volume: 8 Issue: 8 Pages: e72551-e72551
  • DOI: 10.1371/journal.pone.0072551
  • Peer Reviewed
• [Journal Article] Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell- free conditions. (2013)
  • Author(s): Yanagimachi MD, Niwa A, Tanaka T, Ozaki F, Nishimoto S, Murata Y, Yasumi T, Ito J, Tomida S, Oshima K, Asaka I, Goto H, Heike T, Nakahata T, Saito MK
  • Journal Title: PLoS ONE Volume: 8(4) Issue: 4 Pages: e59243-e59243
  • DOI: 10.1371/journal.pone.0059243
  • NAID: 120005244458
  • Peer Reviewed