Expression of connexin 26 and connexin 43 is reduced in Hirschsprung's disease

Coyle, David; Doyle, Brian J.; Murphy, Justin M.; O’Donnell, Anne Marie; Gillick, John; Puri, Prem

doi:10.1016/j.jss.2016.08.010

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…To note that whereas some papers describe Cx43 as the common connexin of both, smooth muscle cells and ICC gap junctions, [43][44][45] others reported a selective Cx43 labelling of the ICC in human bowel. [46][47][48] In our samples of mouse proximal colon, Cx43 labelling was present at the level of the MP and, to a lesser extent, at the border of the SM and in the thickness of the circular muscle layer; the labelling distribution markedly overlapped with that of the three ICC subtypes, as confirmed by the c-Kit antibody labelled twin slices.…”

Section: Discussionsupporting

confidence: 67%

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice

Biagioni,

Traini,

Faussone‐Pellegrini

et al. 2024

J Cellular Molecular Medi

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Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are due to neuropathy. Cisplatin has also antibiotic properties inducing dysbiosis which enhances the inflammatory response, worsening local damage. Thus, a treatment aimed at protecting the microbiota could prevent or reduce the toxicity of chemotherapy. Furthermore, since a healthy microbiota enhances the effects of some chemotherapeutic drugs, prebiotics could also improve this drug effectiveness. We investigated whether chronic cisplatin administration determined morphological and functional alterations in mouse proximal colon and whether a diet enriched in prebiotics had protective effects. The results showed that cisplatin caused lack of weight gain, increase in kaolin intake, decrease in stool production and mucus secretion. Prebiotics prevented increases in kaolin intake, changes in stool production and mucus secretion, but had no effect on the lack of weight gain. Moreover, cisplatin determined a reduction in amplitude of spontaneous muscular contractions and of Connexin (Cx)43 expression in the interstitial cells of Cajal, changes that were partially prevented by prebiotics. In conclusion, the present study shows that daily administration of prebiotics, likely protecting the microbiota, prevents most of the colonic cisplatin‐induced alterations.

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Section: Discussionsupporting

confidence: 67%

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice

Biagioni,

Traini,

Faussone‐Pellegrini

et al. 2024

J Cellular Molecular Medi

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“…The connexin43 (Cx43), which widely exists between ICCs or ICCs and SMCs, is the most important protein of gap junctions in mediating synchronized contraction of SMCs and ICCs function [18,19]. Studies of Hirschsprung’s disease over the past decades have exhibited that lack of Cx43-based communication between ICCs or/and SMCs may be partly responsible for the GI motility disorders [20,21]. McClain et al [22] showed that Ca 2+ responses in enteric glia, mediated by Cx43 hemichannels, influenced gut motility and intestinal transit in mice.…”

Section: Introductionmentioning

confidence: 99%

Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract

Sun

et al. 2018

Aging

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Aging is a significant risk factor for gastrointestinal dysmotility, but aging-associated differences between different organs and the exact time to start degenerating have remained obscure. Here we evaluated alterations of interstitial cells of Cajal, enteric neurons and connexin43 expression in the stomach, jejunum and colon in 2-, 12-, 16-, 20- and 24-month-old mice, as well as in aged human colon. Interstitial cells of Cajal, cholinergic and nitrergic neurons within the whole digestive tract were reduced over time, but their loss first appeared in stomach, then in intestine, helping to understand that gastric function was first impaired during aging. The decrease of connexin43 expression occurred before interstitial cells of Cajal and neurons loss, suggesting that connexin43 might be the major target influenced during senescence. Furthermore, changes in expressions of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, interleukin-6) and apoptosis-related proteins (B-cell lymphoma-2, caspase-3) which indicated “inflammaging”, might contribute to the loss of enteric neurons and interstitial cells of Cajal in aged gastrointestinal tract. Our results provide possible therapeutic time window for beneficial intervention for geriatric patients with gastrointestinal motility disorders.

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“…Moreover, our study for the first time demonstrated that the decreased UBR4 expression also occurred in the ganglionic colon of HSCR patients. It has been shown that several aberrant gene expressions, including SK3 [9, 17], Cx26 and Cx43 [18], and NOS [19], were significantly associated with the persistent intestinal symptoms in HSCR patients after an appropriately completed surgery. Whether the aberrant UBR4 expression in the ganglionic colon is also correlated with the persistence of bowel symptoms after pull-through in HSCR patients warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Aberrant UBR4 expressions in Hirschsprung disease patients

et al. 2019

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BackgroundRecently, pathogenic alleles within ubiquitin N-recognin domain-containing E3 ligase 4 (UBR4) gene have been shown to be associated with Hirschsprung disease (HSCR). We determined the UBR4 expressions in Indonesian HSCR patients.MethodsWe analyzed the UBR4 expressions in the colons of HSCR patient and anorectal malformation (ARM) patient as control by real-time polymerase chain reaction (qPCR).ResultsThirty-seven patients with non-syndromic HSCR and eighteen controls were involved in this study. qPCR revealed that the UBR4 expression was strongly decreased (0.77-fold) in the ganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.43 ± 0.36 vs. 2.05 ± 0.69; p = 0.009), whereas the UBR4 expression was also significantly reduced (0.79-fold) in the aganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.39 ± 0.46 vs. 2.05 ± 0.69; p = 0.044). However, the UBR4 expression change was not associated with gender (p = 0.35 and 0.80), nor with degree of aganglionosis both in ganglionic and aganglionic colons (p = 0.72 and 0.73), respectively.ConclusionOur study demonstrates that expression of UBR4 is decreased in both aganglionic and ganglionic colon of HSCR patients.

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Expression of connexin 26 and connexin 43 is reduced in Hirschsprung's disease

Cited by 9 publications

References 26 publications

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice

Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract

Aberrant UBR4 expressions in Hirschsprung disease patients

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