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腎尿細管上皮細胞の増殖制御機構の研究

Research Project

Project/Area Number 02454372
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionNagasaki University

Principal Investigator

斉藤 泰  長崎大学, 医学部, 教授 (70039832)

Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1990: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywords肝由来尿細管細胞増殖因子 / 上皮成長因子 / トランスフォーミング増殖因子-β / 塩基性線維芽細胞増殖因子 / 肝細胞増殖因子 / 培養尿細管細胞 / 代償性腎成長 / 急性尿細管壊死 / 急性腎不全モデル / インタ-ロイキン1β / インタ-ロイキン6 / トランスフォ-ミング増殖因子ーβ / 代償性腎過形成 / トランスフォ-ミング増殖因子 / 肝由来尿細管細胞増殖抑制因子
Research Abstract

1.一側腎摘出後のウサギ肝に、術後3〜5日目に尿細管細胞の増殖を促進あるいは抑制する物質が見つかった。これらのうち増殖促進因子は分子量15-20KDa、等電点は陰イオンクロマトグラフィー上ほぼ中性領域にあり、単離ウサギ腎皮質尿細管細胞ばかりでなくLLC-PK_1やLLC-RK_1といったブタやウサギの株化尿細管の増殖をも促進したが、正常ラット肝実質細胞やBalb/c3T3線維芽細胞の増殖には影響なく、この因子は腎尿細管細胞特異的に作用する可能性があり、将来急性腎不全の治療への応用も考えられる。
2.腎それ自体に様々な増殖因子が存在する。それらのうち上皮成長因子は代償性腎成長において早期一過性残存腎で増加し、抗EGF抗体によって尿細管細胞の過形成が抑制されたことから、代償性腎成長において上皮成長因子(EGF)は尿細管細胞の増殖に大きく関与していると考えられる。トランスフォーミング増殖因子-β(TGF-β)は、尿細管細胞の機能を高めながらその増殖は抑制する。この因子は尿細管細胞自身が産生しており一側腎摘出後の過形成が終了する頃近位尿細管細胞に認められることから代償性腎成長のブレーキとして、あるいは肥大に関与している可能性がある。塩基性線維芽細胞増殖因子は尿細管細胞の増殖のみでなく腎癌細胞の増殖をも促進する。さらにこの因子は腎癌組織で強く発現しており、腎細胞癌のオートクリン増殖と血管新生に関与していることが示唆された。肝細胞増殖因子は肝再生の強力な促進因子として知られているが、この因子は肝実質細胞ばかりでなく、腎尿細管細胞の強力な増殖促進因子であり、しかも急性尿細管壊死後その活性もmRNAの発現も著しく増加することから、尿細管細胞の再生に大きく関与していることがわかった。

Report

(3 results)
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] SHIGERU KANDA: "A study of growth regulators of renal cortical tubular cells in the rabbit liver." Kidney International. 37. 875-879 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "The effect of transforming growth factor-β on the alkaline phosphatase activity in rabbit renal cortical tubular cell cultures." Cell Biology International Reports. 14. 877-885 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] TSUKASA IGAWA: "Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epitherial cells." Biochemical and Biophysical Research Communications. 174. 831-838 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse." Acta Endocrinologica. 124. 188-193 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells." The Japanese Journal of Nephrology. 34. 19-25 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] JIRO EGUCHI: "Gene expression and innumohistochemical localization of basic fibroblast growth factor in renal cell carcinoma." Biochemical and Biophysical Research Communications. 183. 937-944 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "Anti-epidermal growth factor antibody inhibit compensatory renal hyperplasia but hypertrophy after unilateral nephrectomy in mice." Biochemical and Biophysical Research Communications. 187. 1015-1021 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "Transforming growth factor-β-like activity is secreted by rabbit renal cortical tubular cells in primary culture." Cell Biology. 16. 613-623 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] SHIGERU KANDA: "Transforming growth factor-β in rat kidney during compensatory renal growth." Growth Regulation. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] TSUKASA IGAWA: "Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acutely induced renal injury." American Journal of Physiology. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Igawa,T.,Kanda,S.,Kanetake,H.,Saito,Y.,Ichihara,A.,Tomita,Y.,Nakamura,T.: "Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells." Biochemical and Biophysical Research Communication. 174. 831-838 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kanda,S.,Saha,P.K.Nomata,K.,Taide,M.,Nishimura,N.,Igawa,T.,Yamada,J.,Kanetake,H.,and Saito,Y.: "Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse." Acta Endocrinologica. 124. 188-193 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 神田 滋,金武 洋,斉藤 泰: "代償性腎成長のメカニズムー培養尿細管細胞を用いてー" 西日本泌尿器科. 53. 471-476 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 神田 滋,井川 掌,野俣 浩一郎,金武 洋,斉藤 泰: "培養尿細管細胞の増殖制御因子について" Progress in Medicine. 11. 3167-3169 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kanda,S.,Taide,M.,Igawa,T.,Saha,P.K.,Nishimura,N.,Nomata,K.,Kanetake,H.,Saito,Y.: "Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells." Japanese Journal of Nephrology. 34. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Igawa,T.,Kanda,S.,Kanetake,H.,Saito,Y.,matsumoto,K.,Nakamura,T: "HGF may act as a renotropic factor for renal regeneration after various kidney injuries." Kidney International. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Kanda,K.Nomata,P.K.Saha,N.Nishimura,J.Yamada,H.Kanetake Y.Saito: "A study of growth regulators of renal cortical tubular cells in the rabbit liver." Kidney International. 37. 875-879 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Kanda,T.Igawa,M.Taide P.K.Saha,N.Nishimura,K.Nomata,H.Kanetake Y.Saito: "The effect of transforming growth factorーβ on the alkaline phosphatase activity in rabbit renal cortical tubular cell culture." Cell Biology International Reports. 14. 877-885 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Kanda,P.K.Saha,K.Nomata,M.Taide,N.Nishimura,T.Igawa,J.Yamada,H.Kanetake,Y.Saito: "Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse." Acta Endocrinologica. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Igawa,S.Kanda,H.Kanetake,Y.Saito,A.Ichihara,Y.Tomida,T.Nakamura: "Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells." Biochemical and Biophysical Research Communication. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Tomida,X.Huang,T.Ando,N.Komi,S.Kanda,Y.Saito,A.Ichihara: "Ditribution of hepatocyte growth factor in virous rat tissues." Cell Structure and Function. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 神田 滋・金武 洋・斉藤 泰: "代償性腎成長のメカニズムー培養尿細管細胞を用いてー" 西日本泌尿器科. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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