J Neurogastroenterol Motil.  2020 Jan;26(1):106-116. 10.5056/jnm19099.

Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

Affiliations
  • 1Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
  • 2Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
  • 3Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 4Departments of Pathology, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
  • 5Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam-do, Korea

Abstract

Background/Aims
Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex.
Methods
From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay.
Results
TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001).
Conclusion
Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

Keyword

Cytokines; Irritable bowel syndrome; Sex; Subtype; Tight junctions
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