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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

 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 
 Digestive Diseases and Sciences, Vol.63(3) : 619-627, 2018 
Journal Title
 Digestive Diseases and Sciences 
Issue Date
Animals ; Newborn Animals ; Biomarkers/metabolism ; Diarrhea/enzymology/etiology/pathology ; Animal Disease Models ; Female ; Gastrointestinal Motility ; Interstitial Cells of Cajal/*pathology ; Irritable Bowel Syndrome/*enzymology/*etiology/pathology ; Male ; Maternal Deprivation ; Mice ; Inbred C57BL Mice ; Nitric Oxide Synthase/*metabolism ; Psychological/*complications Stress
Interstitial cells of Cajal ; Neonatal maternal separation ; Neuronal nitric oxide synthase ; irritable bowel syndrome
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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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
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