Neuronal Nitric Oxide Synthase Is a Novel Biomarker for the Interstitial Cells of Cajal in Stress-Induced Diarrhea-Dominant Irritable Bowel Syndrome

Da Eun Jang, Ji Hyun Bae, Yoo Jin Chang, Yoon Hoo Lee, Ki Taek Nam, Il Yong Kim, Je Kyung Seong, Yong Chan Lee, Su Cheong Yeom

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. Aim: The aim of this study was to discover the novel and reliable biomarker for IBS. Method: In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model. Further assessment was conducted with whole gastrointestinal transit test, quantitative RT-PCR, histological examination, and western blot. Results: Male pups developed symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade inflammation, stool irregularity, and increased bowel motility. NMS stress influenced to the interstitial cells of Cajal (ICC) and induced altered bowel motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS expression was only observed in the ICC of the submucosal plexus of IBS-D mice, and the inhibition of nNOS changed the phenotype from IBS-D to IBS with constipation. Conclusion: Our study demonstrates that early-life stress can influence to ICC and modulate bowel activity and that nNOS might be used as a biomarker for ICC stimulation in IBS.

Original languageEnglish
Pages (from-to)619-627
Number of pages9
JournalDigestive diseases and sciences
Volume63
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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