Scholarlink

<p>Radiation-induced senescence of intestinal epithelial cells plays a crucial role in damaging the intestinal mucosal barrier. Previous studies have implicated Numb in regulating intestinal mucosal barrier homeostasis, while Polo-like kinase 1 (Plk1) facilitates cell cycle recovery following radiation. This study aimed to investigate the impact of Numb on radiation-induced intestinal epithelial cell senescence and mucosal barrier injury through its modulation of Plk1 activity. Numb expression in intestinal epithelial cells of C57BL/6J mice was downregulated via intraperitoneal injection of Numb antisense oligodeoxynucleotides. Inhibition of Numb expression significantly increased intestinal mucosal barrier permeability after radiation exposure, as assessed by the FD40 assay and elevated serum diamine oxidase (DAO) concentration. Concurrently, Numb inhibition led to increased levels of γH2AX, p21, and senescence-associated beta-galactosidase (SA-β-gal), along with enhanced expression of inflammatory factors in intestinal epithelial cells. In vitro experiments demonstrated that Numb knockdown resulted in G2 phase accumulation of colonic cells, promoted cellular senescence, and upregulated senescence-associated inflammatory factors. Furthermore, interfering with Plk1 expression enhanced radiation-induced intestinal cell senescence, whereas Plk1 overexpression reversed the senescence phenotype induced by Numb knockdown. This study highlights an important role for Numb in protecting intestinal mucosal barrier function by suppressing radiation-induced senescence of mucosal epithelial cells. Modulation of the Numb-Plk1 signaling pathway represents a potential therapeutic strategy for radiation enteritis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Numb mitigates intestinal epithelial cell senescence induced by radiation through a PLK1-dependent pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月27日

查看全文
  • Yongtao Yang,
  • Xiao Hu,
  • Yuwei Pan,
  • Wen Ji,
  • Tao Liu,
  • Xi Zheng

摘要

Radiation-induced senescence of intestinal epithelial cells plays a crucial role in damaging the intestinal mucosal barrier. Previous studies have implicated Numb in regulating intestinal mucosal barrier homeostasis, while Polo-like kinase 1 (Plk1) facilitates cell cycle recovery following radiation. This study aimed to investigate the impact of Numb on radiation-induced intestinal epithelial cell senescence and mucosal barrier injury through its modulation of Plk1 activity. Numb expression in intestinal epithelial cells of C57BL/6J mice was downregulated via intraperitoneal injection of Numb antisense oligodeoxynucleotides. Inhibition of Numb expression significantly increased intestinal mucosal barrier permeability after radiation exposure, as assessed by the FD40 assay and elevated serum diamine oxidase (DAO) concentration. Concurrently, Numb inhibition led to increased levels of γH2AX, p21, and senescence-associated beta-galactosidase (SA-β-gal), along with enhanced expression of inflammatory factors in intestinal epithelial cells. In vitro experiments demonstrated that Numb knockdown resulted in G2 phase accumulation of colonic cells, promoted cellular senescence, and upregulated senescence-associated inflammatory factors. Furthermore, interfering with Plk1 expression enhanced radiation-induced intestinal cell senescence, whereas Plk1 overexpression reversed the senescence phenotype induced by Numb knockdown. This study highlights an important role for Numb in protecting intestinal mucosal barrier function by suppressing radiation-induced senescence of mucosal epithelial cells. Modulation of the Numb-Plk1 signaling pathway represents a potential therapeutic strategy for radiation enteritis.