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  2. Pikfyve Deficiency Exacerbates Radiation-induced Intestinal Toxicity.
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  2. Pikfyve Deficiency Exacerbates Radiation-induced Intestinal Toxicity.

Related Experiment Video

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
09:10

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation

Published on: July 27, 2022

PIKfyve Deficiency Exacerbates Radiation-Induced Intestinal Toxicity.

Aoqiang Ji1,2, Xing Shen1, Chunan Zhao1

  • 1Academy of Military Medical Sciences, Academy of Military Science, Beijing 100850, China.

Toxics
|May 27, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

PIKfyve is crucial for intestinal epithelial integrity against radiation damage. Its deletion exacerbates radiation toxicity, increasing mortality and highlighting safety concerns for PIKfyve inhibitors in cancer therapy.

Keywords:
PIKfyveepithelial barrierintestinal acute radiation syndromeradiation countermeasuresradiation toxicologytranslational radiobiology

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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Published on: May 12, 2019

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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
09:10

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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
07:05

Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Published on: May 12, 2019

Area of Science:

  • Molecular biology
  • Radiation oncology
  • Gastroenterology

Background:

  • Intestinal acute radiation syndrome (IARS) is a severe, life-threatening condition with limited treatments.
  • Identifying molecular factors that protect intestinal epithelial cells from radiation is key for developing mitigation strategies.

Purpose of the Study:

  • To investigate the role of PIKfyve, a key enzyme in endolysosomal trafficking, in intestinal response to radiation.
  • To determine if PIKfyve impacts radiation-induced intestinal toxicity.

Main Methods:

  • Used an inducible mouse model with PIKfyve specifically knocked out in intestinal epithelial cells (PIKfyve cKO).
  • Subjected mice to 10 Gy abdominal irradiation and assessed toxicity via histopathology, barrier function tests (FD4 assay), apoptosis markers, and gene expression.
  • Validated findings using small intestinal organoids.
  • Main Results:

    • PIKfyve knockout alone did not affect normal gut structure but severely worsened radiation toxicity.
    • Observed villous atrophy, crypt damage, increased apoptosis, and impaired gut barrier function with elevated inflammatory markers.
    • Transcriptomic data showed enhanced DNA damage signaling and inflammation in PIKfyve-deficient intestines, leading to higher mortality.

    Conclusions:

    • PIKfyve is essential for maintaining intestinal epithelial integrity following radiation exposure.
    • The findings suggest potential risks associated with PIKfyve inhibitors in cancer therapy and identify PIKfyve as a target for mitigating radiation toxicity.