Coculture with Clostridium difficile promotes apoptosis of human intestinal microvascular endothelial cells

J Int Med Res. 2018 Nov;46(11):4731-4739. doi: 10.1177/0300060518799267.

Abstract

Objective: The clostridial triose-phosphate isomerase ( tpi) gene is a housekeeping gene that specifically distinguishes Clostridium difficile from other bacteria. This retrospective cohort study was performed to analyze and compare the TPI protein-positive rates in outpatients and hospitalized patients with and without diarrhea (control group).

Methods: Western blotting, methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and flow cytometry were used to investigate the pathogenic mechanism of C. difficile in the development and progression of diarrhea in patients with inflammatory bowel disease (IBD).

Results: The TPI protein-positive rates were significantly higher in patients with diarrhea but without IBD than in the healthy control group as well as in patients with diarrhea and IBD than in patients with diarrhea but without IBD. Coculture with C. difficile inhibited aquaporin-1 protein expression in human intestinal microvascular endothelial cells, which significantly reduced the proliferation of these cells and promoted their apoptosis.

Conclusions: Clostridium difficile infection is associated with diarrhea and may be an important risk factor for diarrhea in patients with IBD. Coculture with C. difficile may inhibit the proliferation of intestinal mucosal cells and promote their apoptosis, reduce intestinal aquaporin-1 expression, and inhibit intestinal water uptake. Clostridium difficile is one cause of C. difficile-associated diarrhea.

Keywords: Clostridium difficile; aquaporin; coculture; diarrhea; inflammatory bowel disease; triose-phosphate isomerase.

MeSH terms

  • Apoptosis*
  • Aquaporin 1 / metabolism
  • Cell Cycle
  • Cell Proliferation
  • Clostridioides difficile / growth & development*
  • Coculture Techniques
  • Diarrhea / complications
  • Diarrhea / microbiology
  • Endothelial Cells / microbiology*
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / microbiology
  • Microvessels / pathology*
  • Triose-Phosphate Isomerase / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • bcl-2-Associated X Protein
  • Aquaporin 1
  • Triose-Phosphate Isomerase