Intestinal epithelial organoids: regeneration and maintenance of the intestinal epithelium

Oda, Mayumi; Hatano, Yoshiko; Sato, Toshiro

doi:10.1016/j.gde.2022.101977

Cited by 11 publications

(10 citation statements)

References 45 publications

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“…Colonic organoids are three-dimensional cultures derived from the epithelium that can be propagated in vitro (19, 20). To determine whether the reduced MUC5B phenotype in UC patient colons is maintained in organoids, we established independent cultures from non-IBD control (n=3) and inflamed UC (n=3) colons.…”

Section: Resultsmentioning

confidence: 99%

Mucin MUC5B levels are reduced in the colonic epithelia of ulcerative colitis patients

Ding,

Koltun,

Yochum

2024

Preprint

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Background & AimsUlcerative colitis (UC) is an inflammatory bowel disease (IBD) where a defect in the colonic epithelial barrier elicits a chronic and unresolved inflammatory response against luminal microbiota. Mucins are heavily glycosylated proteins secreted by goblet cells that form gelatinous layers to protect the colonic epithelium. Whereas the role of the major colonic mucin, MUC2, is established in UC, few reports have analyzed MUC5B in this disease. In this study, we investigated MUC5B expression in colonic tissues and organoid cultures from UC patients and non-IBD controls.MethodsMUC5Btranscripts were analyzed in colonic regions from UC patients and controls using RT-qPCR. MUC5B protein levels in colonic tissues were analyzed and quantified by immunohistochemistry. Patient-derived epithelial organoids were stained for MUC5B, E-cadherin and F-actin. Organoids were treated with interleukin 1 beta (IL-1β) andMUC5Btranscripts were analyzed by RT-qPCR. MUC5B proteins were assessed in IL-1β-treated organoids by immunofluorescent microscopy.ResultsMUC5Btranscripts and proteins were expressed in the healthy colon and their levels were decreased in UC tissues. MUC5B proteins were reduced in organoids derived from UC tissues. IL-1β treatment of control organoids stimulated expression of acidic mucins,MUC5Btranscripts and MUC5B proteins.MUC5Btranscripts were not induced by IL-1β in UC-derived organoids.ConclusionsMUC5B levels are reduced in UC colons and its expression is induced by the IL-1β pro-inflammatory cytokine. These results suggest that MUC5B contributes to the protective colonic mucin layer and that this function is likely compromised in UC.

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Section: Resultsmentioning

confidence: 99%

Mucin MUC5B levels are reduced in the colonic epithelia of ulcerative colitis patients

Ding,

Koltun,

Yochum

2024

Preprint

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“…Our in vivo and in vitro experiments showed that the addition of XAV939 could not reverse the decrease in PPAR-γ and Villin, indicating that XAV939 cannot reverse the differentiation of enterocytes. Within the intestinal tract, enterocytes serve as a vital barrier, responsible for both nutrient absorption and defense against harmful microbial invasion [29] . Multiple studies have consistently demonstrated that UC is associated with the loss of colonic crypt structures, and disruption of enterocytes signi cantly impacts intestinal absorption and compromises the barrier function of the intestine [30][31] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Wnt/β-catenin Signaling Pathway via XAV939 does not mitigate Dextran Sulfate Sodium-Induced Ulcerative Colitis Running Title: XAV939 does not mitigate Ulcerative Colitis

Liang,

Wang,

Mao

et al. 2024

Preprint

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The Wnt/β-catenin signaling pathway is known to be hyperactivated during the pathogenesis of ulcerative colitis (UC). This study aimed to explore the therapeutic efficacy of the Wnt/β-catenin signaling inhibitor, XAV939, in mitigating UC symptoms. Utilizing a dextran sulfate sodium (DSS)-induced UC mouse model, we aimed to evaluate the impact of XAV939 on intestinal morphology through hematoxylin and eosin (HE) staining and to measure the expression levels of critical proteins within the Wnt/β-catenin signaling cascade. Contrary to our expectations, XAV939 did not exert a significant influence on the morphological features and inflammatory status of the intestinal epithelium. Nonetheless, XAV939 was found to effectively suppress the Wnt/β-catenin signaling pathway and its downstream target SOX9. This suppression implies a reduction in the differentiation of intestinal stem cells (ISCs) into secretory cell progenitor cells. Additionally, XAV939 was ineffective in reversing the DSS-induced decline of Villin and PPAR-γ, suggesting that it does not facilitate the differentiation of intestinal absorptive cells. Our findings indicate that the Wnt/β-catenin signaling pathway may not be the predominant mechanism in the pathogenesis of DSS-induced UC.

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“…Organoids derived from intestinal staminal cells can be used to study the intestinal epithelium in several diseases ( 46 , 47 ). In this study, organoids were derived from controls and CD biopsies, and it was observed that, without any treatment, the CD organoids are inflamed and more sensitive to P31-43 stimuli compared to CTR organoids.…”

Section: Discussionmentioning

confidence: 99%

The protective role of Lactobacillus rhamnosus GG postbiotic on the alteration of autophagy and inflammation pathways induced by gliadin in intestinal models

et al. 2023

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Celiac disease (CD) is an autoimmune enteropathy caused by an abnormal immune response to gliadin peptides in genetically predisposed individuals. For people with CD, the only available therapy thus far is the lifelong necessity for a gluten-free diet (GFD). Innovative therapies include probiotics and postbiotics as dietary supplements, both of which may benefit the host. Therefore, the present study aimed to investigate the possible beneficial effects of the postbiotic Lactobacillus rhamnosus GG (LGG) in preventing the effects induced by indigested gliadin peptides on the intestinal epithelium. In this study, these effects on the mTOR pathway, autophagic function, and inflammation have been evaluated. Furthermore, in this study, we stimulated the Caco-2 cells with the undigested gliadin peptide (P31-43) and with the crude gliadin peptic-tryptic peptides (PTG) and pretreated the samples with LGG postbiotics (ATCC 53103) (1 × 108). In this study, the effects induced by gliadin before and after pretreatment have also been investigated. The phosphorylation levels of mTOR, p70S6K, and p4EBP-1 were increased after treatment with PTG and P31-43, indicating that the intestinal epithelial cells responded to the gliadin peptides by activating the mTOR pathway. Moreover, in this study, an increase in the phosphorylation of NF-κβ was observed. Pretreatment with LGG postbiotic prevented both the activation of the mTOR pathway and the NF-κβ phosphorylation. In addition, P31-43 reduced LC3II staining, and the postbiotic treatment was able to prevent this reduction. Subsequently, to evaluate the inflammation in a more complex intestinal model, the intestinal organoids derived from celiac disease patient biopsies (GCD-CD) and controls (CTR) were cultured. Stimulation with peptide 31-43 in the CD intestinal organoids induced NF-κβ activation, and pretreatment with LGG postbiotic could prevent it. These data showed that the LGG postbiotic can prevent the P31-43-mediated increase in inflammation in both Caco-2 cells and in intestinal organoids derived from CD patients.

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Intestinal epithelial organoids: regeneration and maintenance of the intestinal epithelium

Cited by 11 publications

References 45 publications

Mucin MUC5B levels are reduced in the colonic epithelia of ulcerative colitis patients

Mucin MUC5B levels are reduced in the colonic epithelia of ulcerative colitis patients

Inhibition of Wnt/β-catenin Signaling Pathway via XAV939 does not mitigate Dextran Sulfate Sodium-Induced Ulcerative Colitis Running Title: XAV939 does not mitigate Ulcerative Colitis

The protective role of Lactobacillus rhamnosus GG postbiotic on the alteration of autophagy and inflammation pathways induced by gliadin in intestinal models

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