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Digestive Diseases and Sciences

, Volume 63, Issue 3, pp 619–627 | Cite as

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 YeomEmail author
Original Article

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.

Keywords

Interstitial cells of Cajal irritable bowel syndrome Neonatal maternal separation Neuronal nitric oxide synthase 

Notes

Acknowledgments

This study was supported by the Korea Food and Drug Administration Grant (13182KFDA660 and 14182KFDA978) funded by the Korea government.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10620_2018_4933_MOESM1_ESM.pdf (212 kb)
Supplementary material 1 (PDF 212 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate School of International Agricultural TechnologySeoul National UniversityPyeongchangRepublic of Korea
  2. 2.Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and TechnologySeoul National UniversityPyeongchangRepublic of Korea
  3. 3.Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Department of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea
  5. 5.Yonsei UniversitySeoulRepublic of Korea

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