Thyroid hormone receptor protects against kidney injury by inhibiting tubular cell apoptosis

• Project/Area Number: 15K09424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of Yamanashi
• Principal Investigator: FURUYA Fumihiko 山梨大学, 大学院総合研究部, 講師 (90456450)
• Co-Investigator(Kenkyū-buntansha): 高橋 和也 山梨大学, 大学院総合研究部, 助教 (00646135) ; 北村 健一郎 山梨大学, 大学院総合研究部, 教授 (10304990)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 慢性炎症 / 甲状腺ホルモン / 尿細管障害 / 慢性腎臓病

Outline of Final Research Achievements

Compared with wild type mice, TR -deficient irradiated chimeric mice showed exacerbated tubulointerstitial injury in the unilateral ureteral obstruction (UUO) model and macrophages isolated from obstructed kidneys of mice lacking TR displayed increased expression of proinflammatory cytokines such as IL-1β. In bone marrow-derived macrophages from wild type mice, T3-depleted culture medium augmented the phosphorylation of IκBα and enhanced the translocation of p65 to the nucleus via a MAPK/MAPK phosphatase pathway. TR -deficient macrophages also increased the release of proinflammatory cytokines that was accompanied by increased nuclear translocation of p65 compared to wild type macrophages. Comparison of TR -deficient bone marrow-derived macrophages with wild-type macrophages confirmed the propensity of these cells to produce exaggerated levels of IL-1β, and their co-culture with renal epithelial cells induced more severe damage to the epithelial cells .

Research Products

• [Journal Article] The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities. (2017)
  • Author(s): Furuya, Fumihiko Ishii, Toshihisa Tamura, Shogo Takahashi, Kazuya Kobayashi, Hidetoshi Ichijo, Masashi Takizawa, Soichi Kaneshige, Masahiro Suzuki-Inoue, Katsue Kitamura, Kenichiro
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 43960-43960
  • DOI: 10.1038/srep43960
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Thyroid ultrasound findings in a follow-up survey of children from three Japanese prefectures: Aomori, Yamanashi, and Nagasaki (2015)
  • Author(s): Hayashida N, Imaizumi M, Shimura H, Furuya F, Okubo N, Asari Y, Nigawara T, Midorikawa S, Kotani K, Nakaji S, Ohtsuru A, Akamizu T, Kitaoka M, Suzuki S, Taniguchi N, Yamashita S, Takamura N
  • Journal Title: Sci. Rep. Volume: 12 Pages: 9046-9046
  • NAID: 120006987130
  • Peer Reviewed / Open Access
• [Journal Article] Effects of 3,3',5-triiodothyronine on microglial functions. (2015)
  • Author(s): Mori Y, Tomonaga D, Kalashnikova A, Furuya F, Akimoto N, Ifuku M, Okuno Y, Beppu K, Fujita K, Katafuchi T, Shimura H, Churilov LP, Noda M.
  • Journal Title: Glia Volume: 63 Pages: 906-920
  • Peer Reviewed
• [Presentation] Activation of the RhoB signaling pathway by thyroid hormone receptor β (2015)
  • Author(s): 古屋文彦
  • Organizer: 第58回日本甲状腺学会
  • Place of Presentation: 福島県文化センター(福島県福島市)
  • Year and Date: 2015-11-05
  • Int'l Joint Research / Invited
• [Remarks] 山梨大学第三内科研究業績
  • URL: http://yamanashi-3nai.com/research/index02.php