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BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation.

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Summary
This summary is machine-generated.

Blood vessel epicardial substance (BVES) is crucial for maintaining intestinal homeostasis. Loss of BVES in mice leads to expanded intestinal stem cells and enhanced Wnt signaling, improving radiation injury recovery.

Keywords:
Blood vessel epicardial substanceRadiation biologyRadiation enteritisStem cellsWnt signaling

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Area of Science:

  • Gastroenterology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Blood vessel epicardial substance (BVES) is a transmembrane protein implicated in malignancies and epithelial-to-mesenchymal transition.
  • BVES regulates the Wnt pathway, a key modulator of intestinal stem cell programs.
  • The role of BVES in small intestinal (SI) biology and homeostasis, particularly after radiation injury, is largely unexplored.

Purpose of the Study:

  • To investigate the role of BVES in regulating intestinal stem cell programs.
  • To determine the function of BVES in maintaining SI homeostasis following radiation injury.

Main Methods:

  • Utilized Bves(-/-) knockout mice and Lgr5-EGFP reporter mice.
  • Employed ex vivo 3D-enteroid cultures to assess stem cell function.
  • Analyzed crypt height, proliferation, stem cell marker expression (Lgr5, Ascl2, Bmi1, TERT), and Wnt signaling pathway activity.

Main Results:

  • Bves(-/-) mice exhibited increased crypt height, proliferation, and Lgr5+ stem cell populations at baseline.
  • Bves(-/-) enteroids displayed enhanced stemness, proliferation, Wnt signaling, and Wnt activation responsiveness.
  • Post-radiation, Bves(-/-) mice showed improved SI crypt viability, proliferation, and amplified Wnt signaling compared to WT mice.

Conclusions:

  • BVES is a critical regulator of intestinal stem cell programs and SI mucosal homeostasis.
  • Deletion of BVES enhances stem cell function and Wnt signaling, conferring resistance to radiation injury.
  • BVES plays a significant role in the response and recovery of the small intestine after radiation exposure.