The Role and Function of Mucins and Its Relationship to Inflammatory Bowel Disease

Kang, Youra; Park, Hyeonjeong; Choe, Byung-Ho; Kang, Ben

doi:10.3389/fmed.2022.848344

Cited by 52 publications

(44 citation statements)

References 76 publications

(72 reference statements)

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“…As a central and vital signal transduction pathway in many biological and physiological processes, the PI3K-Akt signaling pathway has a relationship with cell proliferation, morphology, apoptosis, migration, and synthesis (29). Besides, the PI3K-Akt signaling pathway has been confirmed to produce a relationship between intestinal health and colonic mucosa by previous references (30,31). In our research, the connection between intestinal barrier function and the PI3K-Akt signaling pathway was confirmed again.…”

Section: Regulation Of Pi K-akt Signaling Pathwaysupporting

confidence: 76%

Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier

et al. 2022

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IntroductionFermented egg-milk peptides (FEMPs) could enhance the colon-intestinal barrier and upgrade the expression of zonula occludens-1 and mucin 2. Besides, the underlying biological mechanism and the targets FEMPs could regulate were analyzed in our study.MethodsHerein, the immunofluorescence technique and western blot were utilized to evaluate the repair of the intestinal barrier. Network pharmacology analysis and bioinformatics methods were performed to investigate the targets and pathways affected by FEMPs.Results and discussionAnimal experiments showed that FEMPs could restore intestinal damage and enhance the expression of two key proteins. The pharmacological results revealed that FEMPs could regulate targets related to kinase activity, such as AKT, CASP, RAF, and GSK. The above targets could interact with each other. GO analysis indicated that the targets regulated by FEMPs could participate in the kinase activity of the metabolic process. KEGG enrichment revealed that the core targets were enriched in pathways related to cell apoptosis and other important procedures. Molecular docking demonstrated that FEMPs could bind to the key target AKT via hydrogen bond interactions. Our study combined the experiment in vivo with the method in silico and investigated the interaction between peptides and targets in a pattern of multi-targets and multi-pathways, which offered a new perspective on the functional validation and potential application of bioactive peptides.

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Section: Regulation Of Pi K-akt Signaling Pathwaysupporting

confidence: 76%

Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier

et al. 2022

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“…Nevertheless, changes in protein expression and (Rodriguez-Feo et al, 2015). Among the extracellular components, Muc2 mucin synthesized and secreted in the gut by goblet cells is a key player of the intestinal barrier function (Kang et al, 2022). Altered Muc2 synthesis and, consequently, aberrant mucin assembly induces endoplasmic reticulum stress and promotes colonic inflammation in mice (Heazlewood et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice

et al. 2023

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BackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−).MethodsWild type (WT) and IL-10−/−. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3–V4 regions of 16S rDNA gene.ResultsIL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups—derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result.ConclusionGut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD.

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“…Recent studies using a mouse model deficient in MUC2 highlighted the importance of MUC in maintaining mucosal barrier integrity (Wu et al, 2022). IECs in mice with a MUC2 deficiency lack morphologically distinct goblet cells and show a significant loss of the intestinal epithelial mucosal layer, leading to increased penetrability and the spontaneous development of UC (Kang et al, 2022). In Frontiers in Molecular Biosciences frontiersin.org addition, tissue biopsy samples obtained from patients with clinical UC in either the active or remission stage showed indications of significant loss of the intestinal mucosal mucus layer, which indicated reductions in the number of goblet cells and MUC2 secretion, leading to the loss of the intestinal epithelial mucus layer, which is one of the pathological mechanisms of UC (Bets et al, 2022).…”

Section: Pathophysiological Changes In Uc Mucosal Injury Abnormalitie...mentioning

confidence: 99%

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

Zheng

Duan

Wen

et al. 2022

Front. Mol. Biosci.

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Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with a complex etiology. Intestinal mucosal injury is an important pathological change in individuals with UC. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5+) intestinal stem cells (ISCs) exhibit self-renewal and high differentiation potential and play important roles in the repair of intestinal mucosal injury. Moreover, LGR5+ ISCs are intricately regulated by both the Wnt/β-catenin and Notch signaling pathways, which jointly maintain the function of LGR5+ ISCs. Combination therapy targeting multiple signaling pathways and transplantation of LGR5+ ISCs may lead to the development of new clinical therapies for UC.

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The Role and Function of Mucins and Its Relationship to Inflammatory Bowel Disease

Cited by 52 publications

References 76 publications

Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier

Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier

Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

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