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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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Irradiation Induces Epithelial Cell Unjamming.

Michael J O'Sullivan1, Jennifer A Mitchel1, Amit Das2

  • 1Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, United States.

Frontiers in Cell and Developmental Biology
|March 3, 2020
PubMed
Summary

Ionizing radiation (IR) can cause epithelial cells to transition from a jammed to an unjammed state, characterized by increased cell motility. This radiation-induced unjamming is dependent on TGF-β receptor activity.

Keywords:
cancerepitheliumirradiationmetastasismigrationunjamming

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Area of Science:

  • Cell biology
  • Radiation biology
  • Biophysics

Background:

  • Epithelial layers are typically quiescent and solid-like but can become dynamic and migratory under various conditions.
  • This epithelial-mesenchymal transition (EMT)-like phenomenon, termed unjamming, is observed in development, injury, and disease models.
  • The effect of ionizing radiation (IR) on epithelial layer dynamics, specifically unjamming, remains largely unexplored.

Purpose of the Study:

  • To investigate whether sub-therapeutic doses of ionizing radiation (IR) can induce an unjamming transition in human bronchial epithelial (HBE) cells.
  • To assess the impact of IR on DNA damage, epithelial integrity, cell differentiation, cell shape, and motility.
  • To elucidate the underlying molecular mechanism of IR-induced epithelial unjamming.

Main Methods:

  • Primary human bronchial epithelial (HBE) cells cultured at an air-liquid interface (ALI) were exposed to 1 Gy of IR.
  • Assessed DNA damage (p-H2AX), epithelial integrity (TEER), and differentiation markers.
  • Measured cell shape changes and cellular migration to evaluate the unjamming transition (UJT).
  • Inhibited TGF-β receptor activity to investigate mechanistic pathways.

Main Results:

  • IR induced significant DNA damage (p-H2AX) but did not compromise epithelial integrity (TEER) or normal cell differentiation.
  • IR exposure led to cell elongation and increased cellular motility, consistent with the unjamming transition.
  • Inhibition of TGF-β receptor activity attenuated the IR-induced migratory response.

Conclusions:

  • Ionizing radiation can provoke an unjamming transition in human bronchial epithelial cells.
  • This radiation-induced unjamming occurs without disrupting epithelial integrity or differentiation.
  • The unjamming effect is mediated through a TGF-β receptor-dependent pathway.