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Molecular mechanisms of glucose transporter alterations and apoptosis progression in intestinal parasitoses

Research Project

Project/Area Number 13470057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 寄生虫学(含医用動物学)
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

ARIZONO Naoki  Kyoto Prefectural University of Medicine, Department of Medical Zoology, Professor, 医学研究科, 教授 (10079725)

Co-Investigator(Kenkyū-buntansha) TEGOSHI Tatsuya  Kyoto Prefectural University of Medicine, Department of Medical Zoology, Assistant, 医学研究科, 助手 (40254370)
UCHIKAWA Ryuichi  Kyoto Prefectural University of Medicine, Department of Medical Zoology, Assistant, 医学研究科, 助手 (80145466)
YAMADA Minoru  Kyoto Prefectural University of Medicine, Department of Medical Zoology, Lecturer, 医学研究科, 講師 (70106392)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordsintestinal parasite / malabsorption / apoptosis / granzyme / Nippostrongylus / glucose transporter / SGLT1 / GLUT5 / 寄生虫 / 小腸 / IEC-6 / カスパーゼ / GLUT / グルコーストランスポーター / gran2yme B
Research Abstract

To determine the cause of malabsorption in intestinal parasitoses, pathological alterations in the intestinal absorptive cells were examined in rats infected with the nematode Nippostrongylus brasiliensis. Nematode infection induced cytopathic alterations and enhanced apoptosis in the intestinal epithelial cells together with the development of villus atrophy. Studies in athymic rnu/rnu and mast cell-deficient Ws/Ws rats revealed that progression of the villus atrophy was dependent on T cells, but not on mast-cell activation, and its occurrence was associated with the increase in number of granzyme B-positive cells in the epithelium and the propria mucosa. T cell-independent cytopathic change was also found, that was possibly associated with TNF up-regulation. In addition, in-vitro studies clarified that N. brasiliensis worms produced and secreted a factor that could induce up-regulation of Fas and apoptosis in the intestinal epithelial cell line IEC-6. N. brasiliensis infection induced hypoglycemia and hypoalbuminemia, and these alterations were associated with decreased expression of glucose transporters SGLT1 and GLUT5,the peptide transporter PepT1,and the amino acid transporter LAT2 in the absorptive cells. These results indicated that nematode infection induces T cell-dependent and -independent apoptosis and cytopathic alterations in the intestinal absorptive cells together with decreased expression of transporter molecules, that could deteriorate nutrient absorption.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yamada M, Uchikawa R, Matsuda S, Arizono N.: "Mechanisms of parasite antigen uptake from the intestine of rats infected with the nematode Nippostrongylus brasihensis."Japanese Journal of Tropical Medicine and Hygiene. 29. 355-359 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hyoh Y, Ishizaka S, Horii T, Fujiwara A, Tegoshi T, Yamada M, Arizono N.: "Activation of caspases in intestinal villus epithelial cells of normal and nematode infected rats."Gut. 50. 71-77 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuroda A, Uchikawa R, Matauda S, Yamada M, Tegoshi T, Arizono N.: "Up-regulation of Fas (CD95) and induction of apoptosis in intestinal epithelial cells by nematode-derived molecules."Infection and Immunity. 70. 4002-4008 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekikawa S.Kawai Y.Fujiwara A, Takeda K.Tegoshia T, Uchikawa R.Yawada M, Arizono N.: "Alterations in hexose, amino acid and peptide transporter expression in intestinal epithelial cells during Nippostrongylus brasiliensis infection in the rat."International Journal for Parasitology. 33. 1419-1426 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiwara A, Kawai Y, Sekikawa S.Horii T, Yamada M, Mitsufuji S, Arizono N: "Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with up-regulation of granzyme B"Journal of Parasitology. 90(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada M, Uchikawa R, Matsuda S, Arizono N.: "Mechanisms of parasite antigen uptake from the intestine of rats infected with the nematode Nippostrongylus brasiliensis."Japanese Journal of Tropical Medicine and Hygiene. 29. 355-359 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hyoh Y, Ishizaka S, Horii T, Fujiwara A, Tegoshi T, Yamada M, Arizono N.: "Activation of caspases in intestinal villus epithelial cells of normal and nematode infected rats."Gut. 50. 71-77 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuroda A, Uchikawa R, Matsuda S, Yamada M, Tegoshi T, Arizono N.: "Up-regulation of Fas (CD95) and induction of apoptosis in intestinal epithelial cells by nematode-derived molecules."Infection and Immunity. 70. 4002-4008 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekikawa S, Kawai Y, Fujiwara A, Takeda K, Tegoshia T, Uchikawa R, Yamada M, Arizonoa N.: "Alterations in hexose, amino acid and peptide transporter expression in intestinal epithelial cells during Nippostrongylus brasiliensis infection in the rat."International Journal for Parasitology. 33. 1419-1426 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lertanekawattana S, Wichatrong T, Chaisari K, Uchikawa R, Arizono N: "Expressions of cytokines and monosaccharide transporters in the duodenal mucosa of gastro-intestinal symptomatic patients in the rural area of Thailand"Japanese Journal of Tropical Medicine and Hygiene. 31. 42 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiwara A, Kawai Y, Sekikawa S, Horii T, Yamada M, Mitsufuji S, Arizono N: "Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with up-regulation of granzyme B"Journal of Parasitology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekikawa S, Kawai Y, Fujiwara A, Takeda K, Tegoshi T, Uchikawa R, Yamada M, Arizon N.: "Alterations in hexose, amino acid and peptide transporter expression in intestinal epithelial cells during Nippostrongylus brasiliensis infection in the rat."International Journal for Parasitology. 33. 1419-1426 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lertanekawattana S, Wichatrong T, Chaisari K, Uchikawa R, Arizono N: "Expressions of cytokines and monosaccharide transporters in the duodenal mucosa of gastro-intestinal symptomatic patients in the rural area of Thailand"Japanese Journal of Tropical Medicine and Hygiene. 31. 42-42 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishida M, Kawai K, Tanaka M, Tegoshi T, Arizono N.: "Expression of E-cadherin in human mast cell line HMC-1"APMIS. 111. 1067-2003 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujiwara A, Kawai Y, Sekikawa S, Horii T, Yamada M, Mitsufuji S, Arizono N: "Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with up-regulation of granzyme B"Journal of Parasitology. 90(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuroda, A.: "Up-regulation of Fas (CD95) and induction of apoptosis in intestinal epithelial cells by nematode-derived molecules"Infection and Immunity. 70・8. 4002-4008 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] ARIZONO, N.: "Glucose transporter gene expressions in intestinal epithelial cells during parasite infection"Abstract book of the 10th international congress of parasitology. 98-98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] ARIZONO, N.: "Up-regulation of Fas (CD95) and induction of apotosis in intestinal epithelial cells by nematode excretory/secretory product"Abstract book of the 10th international congress of parasitology. 153-153 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lentanewkawattana, S.: "Expressions of cytokines and monosaccharide transporters in the duodenal mucosa of patients in the rural area of Thailand"日本熱帯医学雑誌. 30・増. 227-227 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawabata, A.: "Protease-activated receptor 2 (PAR-2) in the pancreas and parotid gland"Life Science. 71・20. 2435-2446 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuda S, Tani Y, Yamada M, Yoshimura K, Arizono N.: "Type 2-biased expression of cytokine genes in lung granulomatous lesions induced by Nippostrongylus brasiliensis infection"Parasite Immunolosy. 23. 219-226 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawabata, A., Kinoshita, M., Nishikawa, H., Kuroda, R., Nishida, M., Araki, H., Arizono, N.他2名: "The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection"Journal of Clinical Investigation. 107. 1443-1450 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hyoh, Y., Ishizaka, S., Horii, T., Fujiwara, A., Tegoshi, T., Yamada, M., Arizono, N.: "Actiration of caspases in intestinal villus epithelial cells of normal and nematode infected rats"GUT. 50. 71-77 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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