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KMID : 1812020190250040589
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Journal of Neurogastroenterology and Motility
2019 Volume.25 No. 4 p.589 ~ p.601
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Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells
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Abstract
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Background/Aims: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility.
Methods: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca2+-activated Cl? (Ano1) channels, and small conductance Ca2+- activated K+ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice.
Results: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions.
Conclusion: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα+) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRαSK3 distribution might be a potential reason for the colonic dysmotility.
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KEYWORD
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Chloride channels, Interstitial cells of Cajal, Small-conductance calcium-activated potassium channels
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