Reduced Stem Cell Factor Links Smooth Myopathy and Loss of Interstitial Cells of Cajal in Murine Diabetic Gastroparesis

Horváth, Viktor J.; Vittal, Harsha; Lörincz, Andrea; Chen, Hui; Almeida‐Porada, Graça; Redelman, Doug; Ördög, Tamás

doi:10.1053/j.gastro.2005.12.027

Cited by 208 publications

(239 citation statements)

References 40 publications

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“…Recent observations indicate that turnover of ICC occurs in immature and adult ICC. 44 -46 However, the factors that regulate this turnover have not been established except that the effects of the receptor tyrosine kinase c-Kit and its ligand, stem cell factor, are known to be required for ICC maintenance 44,[47][48][49] by a still-undefined mechanism.…”

mentioning

confidence: 99%

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

et al. 2007

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confidence: 99%

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

et al. 2007

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“…17,[26][27][28][29][30][31][32][33][34][35][36] Many studies have reported that ICC injury plays an important role in various chronic diseases that cause abnormal gastrointestinal contractions. 27,[29][30][31][32][33]35 In addition, it has been reported that spontaneous contraction signals are transmitted by ICC networks and that the loss of small intestinal motility in humans was caused by reduction in the ICC networks. 37 Furthermore, gastrointestinal smooth muscle is spontaneously active with rhythmic generation of phasic contractions, triggered by ICC distributed in the gut wall.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Park

Kwon

Kim

et al. 2015

J Neurogastroenterol Motil

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Background/Aims Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10 −/− ) mice. Methods Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. Results The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10 −/− mice compared to IL-10 +/+ mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10 −/− mice compared to IL-10 +/+ mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10 −/− mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10 −/− mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. Conclusions These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

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“…Despite the fact that the ICC processes thinned, the hole size metric value of the KO networks did not increase, suggesting a spatial rearrangement of ICC to maintain a consistent spread over adjacent SMC. Spatial remodelling in response to the SMC distribution is feasible, because SMC are primarily responsible for the production of stem cell factor, which is the most important promoter of ICC regeneration and survival [36]. Such a rearrangement rsif.royalsocietypublishing.org J R Soc Interface 10: 20130421…”

Section: Discussionmentioning

confidence: 99%

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

Gao

O’Grady

et al. 2013

J. R. Soc. Interface.

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Depletion of interstitial cells of Cajal (ICC) networks is known to occur in several gastrointestinal motility disorders. Although confocal microscopy can effectively image and visualize the spatial distribution of ICC networks, current descriptors of ICC depletion are limited to cell numbers and volume computations. Spatial changes in ICC network structural properties have not been quantified. Given that ICC generate electrical signals, the organization of a network may also affect physiology. In this study, six numerical metrics were formulated to automatically determine complex ICC network structural properties from confocal images: density, thickness, hole size, contact ratio, connectivity and anisotropy. These metrics were validated and applied in proof-of-concept studies to quantitatively determine jejunal ICC network changes in mouse models with decreased (5-HT 2B receptor knockout (KO)) and normal (Ano1 KO) ICC numbers, and during post-natal network maturation. Results revealed a novel remodelling phenomenon occurring during ICC depletion, namely a spatial rearrangement of ICC and the preferential longitudinal alignment. In the post-natal networks, an apparent pruning of the ICC network was demonstrated. The metrics developed here enabled the first detailed quantitative analyses of structural changes that may occur in ICC networks during depletion and development.

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Reduced Stem Cell Factor Links Smooth Myopathy and Loss of Interstitial Cells of Cajal in Murine Diabetic Gastroparesis

Cited by 208 publications

References 40 publications

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

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