Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice
Lu Chen, Lu Hongli, Huang Xu, Liu Shaohua, Zang Jingyu, Li Yujia, Chen Jie, Xu Wenxie,
소속 상세정보
( Lu Chen )
Shanghai Jiao Tong University School of Medicine Department of Anatomy and Physiology
( Lu Hongli )
Shanghai Jiao Tong University School of Medicine Department of Anatomy and Physiology
( Huang Xu )
Shanghai Jiao Tong University School of Medicine Department of Anatomy and Physiology
( Liu Shaohua )
Shanghai Jiao Tong University School of Medicine South Renji Hospital Department of Anesthesiology
( Zang Jingyu )
Shanghai Jiao Tong University School of Medicine Xin Hua Hospital Department of Pediatric Surgery
( Li Yujia )
Shanghai Jiao Tong University School of Medicine Department of Anatomy and Physiology
( Chen Jie )
Shanghai Jiao Tong University School of Medicine Xin Hua Hospital Department of Pediatric Surgery
( Xu Wenxie )
Shanghai Jiao Tong University School of Medicine Department of Anatomy and Physiology
Abstract
Background/Aims: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice.
Methods: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study.
Results: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice.
Conclusion: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
키워드
Anoctamin-1; Colitis; Interstitial cells of Cajal; Nitric oxide synthase; Down-regulation
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