The Relationship between Mucins and Ulcerative Colitis: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Review Questions
- Does mucin expression and activity change in patients with UC compared to healthy controls?
- How do changes in mucin expression effect mucus structure?
- What impact do these changes have on host-microbiome interactions and inflammation?
2.2. Search Strategy
- Colitis AND mucin *
- (IBD OR Inflammatory Bowel Disease) AND mucin *
- (IBD OR Inflammatory Bowel Disease) AND mucin * degradationTo optimise the retrieval of articles in databases, Boolean operators were used (AND, OR). Using ‘AND’ allows for citations containing all search terms to be retrieved, whereas using ‘OR’ can produce citations containing at least one of a group of search terms. Therefore, ‘OR’ was used here where words were similar/related e.g. IBD and Inflammatory Bowel Disease. Mucin was also truncated (truncation is indicated by Asterix – *) in order to find citations including mucin and all words with the stem ‘mucin’ e.g. mucin, mucins, mucinase.
2.3. Study Selection and Items Collected
2.4. Inclusion & Exclusion Criteria
2.5. Study Quality Assessment
2.6. Data Synthesis
3. Results
3.1. Search Results
3.2. Overview of Studies Selected for Analysis
3.3. Critical Appraisal of Included Studies
3.4. MUC2 Expression in Colitis
3.4.1. MUC2 mRNA Expression
3.4.2. MUC2 Protein Expression
3.4.3. Goblet Cells and MUC2
3.5. Membrane-Associated Mucins in Colitis
3.6. MUC5AC in Colitis
4. Discussion
5. Conclusions
Authors Contribution
Funding
Conflicts of Interest
References
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Identification | Population | Methods Used | |||||
---|---|---|---|---|---|---|---|
First Author, Reference | Year | Country | Control Samples | Nature of Control Samples | Patient Samples | Diagnosis-Disease Severity/Scoring Indices | Study Design |
Weiss, [32] | 1996 | USA | 1 | Resected tissue from patient with colon diverticular disease | 8 | Method of Diagnosis/ Scoring Indices used are not stated | Case–control study |
Tytgat, [33] | 1996 | Netherlands | 7 | Negative history of IBD (colon appeared normal endoscopically and histologically) | Active UC: 6, Inactive UC (remission): 6 | Truelove and Richards Index | Case–control study |
Hinoda, [34] | 1998 | Japan | 14 | Normal colonic tissue obtained post-mortem (from autopsies) | 31 | Matts Score | Case–control study |
Van Klinken, [35] | 1999 | Netherlands | 12 | Tissue resected from patients diagnosed with Irritable Bowel Syndrome, hyperplastic polyps or diverticulosis but with negative history of IBD | Active UC: 13, Inactive UC (remission): 12 | Truelove and Richards | Case–control study |
Hanski, [36] | 1999 | Germany | 13 | Histologically normal mucosae samples | 70 | Matts Score (degree of inflammation), Remmele and Stegner (immunoreactive score for immunohistochemistry) | Case–control study |
Shaoul, [37] | 2004 | Japan | 5 | Samples taken from study groups histology library (original source of controls is not stated) | 5 | Method of Diagnosis/Scoring Indices used are not stated | Case–control study |
Longman, [38] | 2006 | UK | 17 | Tissue resected from patients undergoing elective colorectal resection surgery but with negative history of IBD | 40 | Truelove and Witts Criteria | Case–control study |
Moehle, [39] | 2006 | Germany | 14 | Tissue resected from patients following colonoscopy (8 with no tissue abnormalities; remaining samples from patients with diverticulitis, polyposis coli, lymphoid tissue-lymphoma, carcinoma, diverticulosis, eosinophilic colitis, infectious colitis | Active UC: 14, Inactive UC (remission): 5 | Diagnosis based on clinical features and radiologic/endoscopic findings | Case–control study |
Gersemann, [46] | 2009 | Germany | 21 | Tissue resected from patients undergoing routine colonoscopy (specific reasons for colonoscopy are not outlined) | Active UC: 25Inactive UC: 15 | Method of Diagnosis/Scoring Indices used are not stated | Case–control study |
Furr, [40] | 2010 | USA | 21 | Tissues randomly resected from patients undergoing colonic biopsy but with negative history of IBD | 14 | Diagnosis based on medical records | Case–control study |
Senapati, [47] | 2010 | USA | 12 | Patients undergoing colonoscopy whose colonoscopic exams/histology were normal | 25 | Diagnosis based on medical records | Case–control study |
Larsson, [41] | 2011 | Sweden | 25 | Tissue resected from patients during colonoscopy for polyp surveillance, investigation of anaemia or rectal bleeding (normal colonic mucosa, no signs of inflammation) | Active UC: 15, Inactive UC (remission): 13 | Sandborn’s histological activity score | Case–control study |
Kini, [42] | 2015 | India | 12 | Tissue resected from patients with IBS undergoing routine colonoscopy or during polyp surveillance colonoscopy | 22 | Truelove and Witts (clinical disease severity), Ulcerative Colitis Disease Activity Index (endoscopic severity) | Case–control study |
Yamamoto-Furusho, [43] | 2015 | México | 30 | Tissue resected from patients during colonoscopy for polyp surveillance/screening and evaluation for anaemia (normal colonic mucosa, no signs of inflammation) | Active UC: 20, Inactive UC (remission): 20 | Mayo score (clinical and endoscopic activity evaluation), Riley score (histological activity evaluation) | Case–control study |
Alipour, [44] | 2016 | Canada | 12 | Tissue resected from patients with Irritable bowel syndrome, benign polyps, chronic diarrhoea but negative history of IBD and no signs of inflammation | 10 | Paris Classification and Paediatric Ulcerative Colitis Activity Index (PUCAI) | Case–control study |
van der Post, [45] | 2019 | Sweden | 47 | Tissues resected from patients during colonoscopy; patients with polyps, diverticulosis but with negative history of IBD | Active UC: 36, Inactive UC (remission): 28 | Mayo score (clinical and endoscopic activity evaluation) and/or Sandborn’s histological activity score | Case–control study |
First Author, Reference | Purpose of Study | MUC Gene Investigated | Measuring MUC Expression | Key Findings |
---|---|---|---|---|
Weiss, [32] | To investigate effect of inflammation on expression of mucin genes at cellular level | MUC2, MUC3 | In-situ hybridisation with RNA probes | MUC2 and MUC3 expression in colonic mucosa is independent of inflammation |
Tytgat, [33] | To study regulation of MUC2 expression in patients with UC compared with controls | MUC2 | MUC2 precursor quantified by SDS-PAGE, total MUC2 by dot blot, in-situ hybridisation with RNA probes to quantify MUC2 mRNA | Inefficient translation of MUC2 mRNA may lead to the reduction in MUC2 synthesis observed in active UC |
Hinoda, [34] | To determine if MUC2 protein expression is altered in UC | MUC2 | MUC2 protein detected by Immunohistochemistry | Decreased MUC2 protein production and expression in active UC is associated with undifferentiated goblet cells |
Van Klinken, [35] | To determine whether there are alterations in MU2 sulphation and secretion in active UC | MUC2 | Analysis and quantification of total MUC2 using SDS-PAGE and dot blotting | Absolute amount of MUC2 secreted is decreased and mucins are under-sulphated in active UC |
Hanski, [36] | To study alterations in MUC2 expression in UC patient colonic tissue | MUC2 | MUC2 protein detected by immunohistochemistry and MUC2 mRNA detected using in-situ hybridisation | Increase in MUC2 protein detection in UC samples may be related to reduction in post transcriptional modification |
Shaoul, [37] | To investigate alterations in expression and distribution of MUC2, MUC5AC, trefoil factor 1 (TFF1) in UC | MUC2, MUC5AC | PAS/Alcian blue immunohistochemistry | Immature (poorly glycos-ylated) MUC2 is expressed in UC colonic mucosa depleted of goblet cells |
Longman, [38] | To investigate alterations in the expression of mucin genes and trefoil peptide genes in UC | MUC1-6 | Immunohistochemistry and in-situ hybridisation | MUC1 expression upregulation is associated with severe UC and there is a reduction of MUC2 expression in UC |
Moehle, [39] | To characterize changes in mucin expression and identify allelic variants of MUC genes in UC | MUC1-20 | Affymetrix DNA-microarray analysis and RT-PCR | MUC12 mRNA expression is downregulated in UC and is independent of inflammation |
Gersemann, [46] | To understand the mechanisms involved with goblet cell differentiation and mucin production in IBD | MUC1, MUC2, MUC4 | RT-PCR | Impairments in goblet cell differentiation factor induction in UC correlates with a reduction in mucin synthesis. |
Furr, [40] | To determine whether MUC1 expression is altered in IBD | MUC1 | Immunochemistry using anti-MUC1 anti-bodies | Overexpression and hypoglycosylation of MUC1 observed in a subset of UC patients |
Senapati, [47] | To determine the subcellular localization of MUC17 in colonic mucosa and to determine whether MUC17 expression is altered in IBD and neoplastic diseases. | MUC17 | Immunohistochemistry using anti-MUC17 polyclonal antibody | MUC17 expression is reduced in colonic mucosa of UC patients |
Larsson, [41] | To determine whether MUC2 glycosylation is related to degree of mucosal inflammation in UC | MUC2 | SDS-PAGE used to identify and quantify MUC2 | Alterations in MUC2 glycosylation are associated with inflammation |
Kini, [42] | To determine whether alterations occur in colonic stem cells during the pathogenesis of UC and to determine the impact of such changes on goblet cell development and proteins synthesized by goblet cells | MUC2 | H&E, Alcian blue and PAS immunohistochemistry staining to detect MUC2 protein | A reduction in MUC2 protein within the lower colonic crypt precedes inflammation. |
Yamamoto-Furusho, [43] | To determine if MUC12, MUC16, MUC20 expression changes in UC | MUC12, MUC16, MUC20 | MUC gene expression measured using RT-PCR and MUC protein expression measured using immunohistochemistry | MUC16, MUC20 expression increase in UC and increase in MUC20 was associated with remission of UC |
Alipour, [44] | To assess whether mucosal barrier defects are prerequisites to UC | MUC2 | Fluorescence in-situ hybridisation (FISH) and immunofluorescence | Reduction in mucin-containing goblet cells and mucin production in UC patients compared to controls |
van der Post, [45] | To investigate compositional alterations that occur at the adherent mucus layer in UC | MUC2 | Absolute quantification of MUC2 using Skyline (V.3.6.0.1) following mass spectrometry | Reduction of MUC2 in active UC associated with exhaustion of secretory response of goblet cells to microbes |
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Bankole, E.; Read, E.; Curtis, M.A.; Neves, J.F.; Garnett, J.A. The Relationship between Mucins and Ulcerative Colitis: A Systematic Review. J. Clin. Med. 2021, 10, 1935. https://doi.org/10.3390/jcm10091935
Bankole E, Read E, Curtis MA, Neves JF, Garnett JA. The Relationship between Mucins and Ulcerative Colitis: A Systematic Review. Journal of Clinical Medicine. 2021; 10(9):1935. https://doi.org/10.3390/jcm10091935
Chicago/Turabian StyleBankole, Esther, Emily Read, Michael A. Curtis, Joana F. Neves, and James A. Garnett. 2021. "The Relationship between Mucins and Ulcerative Colitis: A Systematic Review" Journal of Clinical Medicine 10, no. 9: 1935. https://doi.org/10.3390/jcm10091935