Mast1 mediates radiation-induced gastric injury via the P38 MAPK pathway

Exp Cell Res. 2021 Dec 15;409(2):112913. doi: 10.1016/j.yexcr.2021.112913. Epub 2021 Nov 11.

Abstract

Radiation-induced gastric injury is a serious adverse effect and reduces the efficacy of radiotherapy treatment. However, the mechanisms underlying radiation-induced stomach injury remain unclear. Here, mouse stomach and gastric epithelial cells were irradiated with different doses of X-ray radiation. The results showed that radiation induced gastric injury in vivo and in vitro. Differentially expressed functional mRNAs in irradiation-induced gastric tissues were screened from the Gene Expression Omnibus (GEO) database. We found that the expression of microtubule-associated serine/threonine kinase 1 (Mast1) was downregulated in mouse gastric tissues and gastric epithelial cells after irradiation. Furthermore, functional assays showed that knockdown of Mast1 inhibited growth and promoted apoptosis in gastric epithelial cells, while overexpression of Mast1 protected gastric epithelial cells from radiation damage. Mechanistically, Mast1 negatively regulated radiation-induced injury in gastric epithelial cells by inhibiting the activation of P38. The apoptosis caused by knockdown of Mast1 in gastric epithelial cells could be partially reversed by the P38 inhibitor SB203580. Moreover, data from several gastric cancer cell lines and online databases revealed that Mast1 was not involved in the development of gastric cancer. Collectively, our findings demonstrated that Mast1 is essential for radiation-induced gastric injury, providing a promising prognostic and therapeutic target.

Keywords: Gastric injury; MAPK signaling Pathway; Mast1; P38; Radiation.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Stomach / injuries
  • Stomach / metabolism
  • Stomach / pathology*
  • Stomach / radiation effects
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Tumor Cells, Cultured
  • X-Rays / adverse effects*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Microtubule-Associated Proteins
  • MAST1 protein, human
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases