Diabetes‐induced colonic slow transit mediated by the up‐regulation of PDGFRα<sup>+</sup> cells/SK3 in streptozotocin‐induced diabetic mice

Song, Ni-Na; Lu, Hsin-I; Lü, Chen; Tong, Lei; Huang, Shan; Huang, Xu; Chen, J.; Kim, Y.‐C.; Xu, Wen‐Xie

doi:10.1111/nmo.13326

Cited by 17 publications

(27 citation statements)

References 39 publications

(95 reference statements)

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“…PDGFRα + cells express SK3 protein. Inhibitory neurotransmitters, mainly purines bind to G-protein coupled P2Y1 receptors in PDGFRα + cells, 4,9,36 increase intracellular Ca 2+ , activate SK3 channels, and induce hyperpolarization. 37,38 In the present study, western blot displayed that the Pdgfra and SK3 proteins were significantly upregulated in PCO colon compared with those of control mice.…”

Section: Discussionmentioning

confidence: 99%

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

Wang

Zang

Huang

et al. 2019

J Neurogastroenterol Motil

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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), Ca 2+-activated Cl-(Ano1) channels, and small conductance Ca 2+-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. Conclusions 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 PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.

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Section: Discussionmentioning

confidence: 99%

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

Wang

Zang

Huang

et al. 2019

J Neurogastroenterol Motil

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“…Interestingly, although synaptic-like contacts between nerve varicosities and TCs were not observed under the TEM, it has been demonstrated that TCs express purine receptors P2Y1 and apamin-sensitive SK3 channels and respond to agonists and antagonists to these receptors [ 18 , 19 , 41 , 42 , 43 ]. Furthermore, the TCs/PDGFRα-positive cells selectively expressed the SK3 channel among all the ICs present in the gut interstitium [ 44 ] and significant changes in the functionality of these receptors have been associated with GI diseases [ 45 , 46 , 47 ]. TCs also contain soluble guanylyl cyclase and it has been speculated that they could function as neural transducers responding to ATP and nitric oxide [ 19 , 40 ].…”

Section: Telocytesmentioning

confidence: 99%

The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut

Vannucchi

2020

IJMS

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Ten years ago, the term ‘telocyte’ was introduced in the scientific literature to describe a ‘new’ cell type described in the connective tissue of several organs by Popescu and Faussone-Pellegrini (2010). Since then, 368 papers containing the term ‘telocyte’ have been published, 261 of them in the last five years. These numbers underscore the growing interest in this cell type in the scientific community and the general acceptance of the name telocyte to indicate this interstitial cell. Most of these studies, while confirming the importance of transmission electron microscopy to identify the telocytes with certainty, highlight the variability of their immune phenotypes. This variability was interpreted as due to (i) the ability of the telocytes to adapt to the different sites in which they reside; (ii) the distinct functions they are likely to perform; and (iii) the existence of telocyte subtypes. In the present paper, an overview of the last 10 years of literature on telocytes located in the gut will be attempted, confining the revision to the morphological findings. A distinct chapter will be dedicated to the recently hypothesized role of the telocytes the intestinal mucosa. Through this review, it will be shown that telocytes, despite their variability, are a unique interstitial cell.

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“…EFS induced biphasic IJPs in control colonic muscles, consisting of a fast hyperpolarization (fIJP), following with a more stable hyperpolarization reaction (sIJP) that continued till the stimulus ended. 26,27 In the following experiments, the amplitudes of sIJPs were recorded in control and DSS-colitis mice. In the proximal colon of the control mice, EFS (50 V; 3, 6, and 9 Hz; 5 seconds) induced a continuous hyperpolarization after the fIJPs, and the average amplitudes of sIJPs were 3.3 ± 0.3, 7.6 ± 0.4, and 13.7 ± 0.4 mV (n = 7; Fig.…”

Section: Changes In Electrical Field Stimulation-induced Slow Inhibitmentioning

confidence: 99%

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

Lü

Huang

et al. 2019

J Neurogastroenterol Motil

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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.

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Diabetes‐induced colonic slow transit mediated by the up‐regulation of PDGFRα⁺ cells/SK3 in streptozotocin‐induced diabetic mice

Abstract: These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.

Cited by 17 publications

References 39 publications

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

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Diabetes‐induced colonic slow transit mediated by the up‐regulation of PDGFRα+ cells/SK3 in streptozotocin‐induced diabetic mice

Abstract: These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.

Cited by 17 publications

References 39 publications

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells

The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut

Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice

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Diabetes‐induced colonic slow transit mediated by the up‐regulation of PDGFRα⁺ cells/SK3 in streptozotocin‐induced diabetic mice