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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Graduate School of International Agricultural Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea

    Da Eun Jang, Yoo Jin Chang, Yoon Hoo Lee & Su Cheong Yeom

  2. Designed Animal and Transplantation Research Institute, Institute of Greenbio Research and Technology, Seoul National University, 1447 Pyeongchang-Ro, Daewha, Pyeongchang, Gangwon, 25354, Republic of Korea

    Ji Hyun Bae & Su Cheong Yeom

  3. Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 25354, Republic of Korea

    Ki Taek Nam

  4. Department of Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea

    Il Yong Kim & Je Kyung Seong

  5. Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Republic of Korea

    Yong Chan Lee

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  1. Da Eun Jang
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Correspondence to Su Cheong Yeom.

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Jang, D.E., Bae, J.H., Chang, Y.J. et al. Neuronal Nitric Oxide Synthase Is a Novel Biomarker for the Interstitial Cells of Cajal in Stress-Induced Diarrhea-Dominant Irritable Bowel Syndrome. Dig Dis Sci 63, 619–627 (2018). https://doi.org/10.1007/s10620-018-4933-7

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