Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant with chronic idiopathic intestinal pseudoobstruction

Yamataka, Atsuyuki; Ohshiro, Kiyohiko; Kobayashi, Hiroyuki; Lane, Geoffrey J.; Yamataka, T.; Fujiwara, Toshio; Sunagawa, Masakatsu; Miyano, Takeshi

doi:10.1016/s0022-3468(98)90660-1

Cited by 88 publications

(60 citation statements)

References 21 publications

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“…4 In several disorders of gastrointestinal motility, including Hirschsprung's disease, chronic intestinal pseudo-obstruction, slow transit constipation abnormalities are observed in the density and distribution of the c-kit positive cells. [5][6][7] The renal calyces, renal pelvis, UPJ, ureters (proximal to distal), ureteral orifices, fundus and corpus of the bladder in porcines were evaluated by Metzger and colleagues. 8 c-kit expression was examined at the level of mRNA in ureteral tissue and the highest expression of c-kit mRNA was determined to be in the UPJ.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical and electron microscopic examination of Cajal cells in ureteropelvic junction obstruction

Eken

Erdogan

Kuyucu

et al. 2013

CUAJ

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E311Cite as: Can Urol Assoc J 2013;7(5-6):e311-6. http://dx.doi.org/10.5489/cuaj.11293 Published online May 13, 2013 (early released September 10, 2012). AbstractObjective: We examine the ultrastructural configurations of Cajal cells by electron microscopy, as well as the quantitative changes occurring in Cajal cells by light microscopy. Methods: In total, 35 patients with ureteropelvic junction (UPJ) obstruction and 7 patients without obstruction were compared immunohistochemically with c-kit (CD117) to quantify the number of cells. On electron microscopic examination, 7 patients with UPJ obstruction and 3 patients without obstruction were compared to evaluate the changes which occurred in the ultrastructural configuration of the Cajal cells. Results: On light microscopic examination, it was determined that the Cajal cells, which demonstrate c-kit (CD117) immunoreactive character, were located near the circular muscle layer and parallel to the muscle cells. The number of Cajal cells in the control group was significantly increased compared to the number of cells in patients with UPJ obstruction (p < 0.001). On electron microscopic examination, the number of interstitial cells was also higher in the control group. A decrease in the number of the caveolae in these cells was seen in the group with UPJ obstruction compared to the control group. Conclusion: In UPJ obstruction, a decrease in the number of Cajal cells, as well as the changes in the morphologic structure of the Cajal cells, indicates that these cells have a role in the pacemaker system and are associated with ureteral peristalsis.

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Section: Introductionmentioning

confidence: 99%

Immunohistochemical and electron microscopic examination of Cajal cells in ureteropelvic junction obstruction

Eken

Erdogan

Kuyucu

et al. 2013

CUAJ

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“…Elucidating the role of membrane-bound vs. soluble SF in the SF/c-kit signaling pathway in ICC is important, because loss of ICC is observed and may be involved in the pathophysiology of several motility disorders, such as slow transit constipation (8), diabetic gastroenteropathy (9), and pseudoobstruction (38). Loss of ICC may be a primary event or secondary to loss of a signaling molecule, such as SF, from a specific cell type in the gut.…”

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confidence: 99%

Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture

Rich¹,

Miller²,

Gibbons

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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The binding of Steel factor (SF) to c-kit initiates a signaling pathway essential for development and maintenance of interstitial cells of Cajal (ICC). Soluble and membrane-bound isoforms of SF are expressed in the gastrointestinal tract, but the role for either isoform in supporting ICC development is unknown. The aim of this study was to determine the role of SF in supporting ICC in culture. ICC were cultured from dissociated mouse jejunum and grown with fibroblast cell lines that produced either soluble, membrane-bound or membrane-restricted SF. ICC were identified and counted by c-kit immunoreactivity. The number of c-kit immunoreactive cells was greater in the coculture system compared with cultures grown without SF-producing fibroblasts. All forms of SF-producing fibroblasts increased ICC number in culture but physical separation of the fibroblasts from the c-kit immunoreactive cells, the addition of exogenous SF to the culture medium, or fibroblast-conditioned media did not. These results are consistent with the hypothesis that the membrane-bound form of SF preferentially contributes to expression of c-kit-positive ICC under cell culture conditions.

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“…Another subset of patients and animal models have subtle changes in enteric ganglion cell number or other cell types that could not be excluded by the methods used in our study. This includes patients with chronic obstructive symptoms and reduced numbers of ICC, modified smooth muscle cells that function as a "pacemaker" system for the intestinal tract (Faussone-Pellegrini et al, 1999a, 1999bYamataka et al, 1998). Although it is unclear whether changes evident in the ICC of the latter group are primary or secondary to underlying obstructive symptoms, mutations that impair expression of c-kit receptor by ICC lead to loss of these cells and intestinal dysmotility in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory Investigation • March 2001 • Volume 81 • Number 3 Maeda et al, 1992;Torihashi et al, 1995;Ward et al, 1998;Yamataka et al, 1998), we examined c-kit expression in the distal colon of HGF/SF transgenic mice by Northern blot analysis. The level of c-kit expression in the transgenic colon was essentially equal to that in wild-type mice (Fig.…”

Section: Intestinal Dysfunction In Hgf/sf Transgenic Micementioning

confidence: 99%

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

Takayama

Takagi

LaRochelle

et al. 2001

Laboratory Investigation

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SUMMARY:Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of gastrointestinal epithelial cells in vitro;however, the physiological role of HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo function, mice were analyzed in which an HGF/SF transgene was overexpressed throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in this study (28 of 87) died by 6 months of age as a result of sporadic intestinal obstruction of unknown etiology. Enteric ganglia were not overtly affected, indicating that the pathogenesis of this intestinal lesion was different from that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. Expression of interleukin-2 was decreased in the transgenic colon, indicating that HGF/SF may influence regulation of the local intestinal immune system within the colon. These results suggest that HGF/SF plays an important role in the development of gastrointestinal paresis and chronic intestinal inflammation. HGF/SF transgenic mice may represent a useful model for the study of molecular mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. Moreover, our data identify previously unappreciated side effects that may be encountered when using HGF/SF as a therapeutic agent. (Lab Invest 2001, 81:297-305).H epatocyte growth factor/scatter factor (HGF/ SF) was first identified as a highly potent hepatocyte mitogen (Gohda et al, 1988;Nakamura et al, 1989) but is now known as a multifunctional cytokine based on its ability to stimulate proliferation, movement, and/or morphogenesis of a broad spectrum of cultured epithelial cells expressing the tyrosine kinase receptor encoded by the c-met proto-oncogene (Gherardi and Stoker, 1991;Montesano et al, 1991;Rosen et al, 1994;Rubin et al, 1991;Vande Woude, 1992;Zarnegar and Michalopoulos, 1995). HGF/SF is produced in cells of mesenchymal origin, whereas c-met is expressed in adult and embryonic epithelium, implicating HGF/SF-Met signal transduction pathways as important in the epithelial-mesenchymal interaction that occurs during embryogenesis, tissue organization, and organogenesis. Gene targeting studies have shown that HGF/SF-Met signaling is required for the normal development of liver, skeletal muscle, and placenta Schmidt et al, 1995;Uehara et al, 1995).In the fetal digestive tract, c-met transcripts were found in the epithelia of the intestinal anlagen and the villi, whereas the distribution of HGF/SF RNA showed dynamic changes during mouse development by in situ hybridization (Sonnenberg et al, 1993). Immunohistochemical analysis of temporal expression revealed that both HGF/SF and c-Met could be detected between 7 and 8 weeks of gestation in human fetal digestive tissues (Kermorgant et al, 1997). These results suggest that HGF/SF-Met signaling participates in digestive system morphogenesis. Moreover, previous studies demonstrated that HGF/SF can stimulate both esophageal ...

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Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant with chronic idiopathic intestinal pseudoobstruction

Cited by 88 publications

References 21 publications

Immunohistochemical and electron microscopic examination of Cajal cells in ureteropelvic junction obstruction

Immunohistochemical and electron microscopic examination of Cajal cells in ureteropelvic junction obstruction

Local presentation of Steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

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