Tight junction protein changes in irritable bowel syndrome: the relation of age and disease severity

Korean J Intern Med. 2024 Nov;39(6):906-916. doi: 10.3904/kjim.2024.097. Epub 2024 Nov 1.

Abstract

Background/aims: The etiology of irritable bowel syndrome (IBS) is associated with intestinal mucosal barrier damage. However, changes in the tight junction (TJ) proteins in IBS have not been fully elucidated. This study aimed to evaluate TJ protein changes in IBS patients and the relationship between aging and disease severity.

Methods: Thirty-six patients with IBS fulfilling the Rome IV criteria and twenty-four controls were included. To evaluate the change of TJ in the colonic mucosa, quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry (IHC) were performed, respectively.

Results: The entire IBS group (n = 36) exhibited decreased levels of claudin-1 and -2 mRNA compared to the control group (n = 24), with statistical significance (p < 0.05). Additionally, in western blot analyses, both claudin-1 and ZO-1 levels were significantly reduced in the IBS group compared to the control group (n = 24) (p < 0.05). IHC analysis further revealed that ZO-1 expression was significantly lower in the IBS group than in the control group (p < 0.001). This trend of reduced ZO-1 expression was also observed in the moderate-to-severe IBS subgroup (p < 0.001). Significantly, ZO-1 expression was notably lower in both the young- (p = 0.036) and old-aged (p = 0.039) IBS groups compared to their respective age-matched control groups. Subtype analysis indicated a more pronounced decrease in ZO-1 expression with advancing age.

Conclusion: ZO-1 expression was especially decreased in the aged IBS group. These results suggest that ZO-1 might be the prominent TJ protein causing IBS in the aging population.

Keywords: Aging; Colon; Irritable bowel syndrome; Tight junction.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Case-Control Studies
  • Claudin-1* / genetics
  • Claudin-1* / metabolism
  • Claudin-2 / genetics
  • Claudin-2 / metabolism
  • Claudins
  • Colon / metabolism
  • Colon / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa* / metabolism
  • Intestinal Mucosa* / pathology
  • Irritable Bowel Syndrome* / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Severity of Illness Index*
  • Tight Junctions / metabolism
  • Tight Junctions / pathology
  • Young Adult
  • Zonula Occludens-1 Protein* / analysis
  • Zonula Occludens-1 Protein* / genetics
  • Zonula Occludens-1 Protein* / metabolism

Substances

  • Claudin-1
  • CLDN1 protein, human
  • Zonula Occludens-1 Protein
  • TJP1 protein, human
  • CLDN2 protein, human
  • Claudin-2
  • RNA, Messenger
  • Claudins