Modulation of Mucin ( MUC2, MUC5AC  and  MUC5B ) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A

Author(s): Xin Huang ¹ ^, ² ^, ³ ^, ⁴ , Yanan Gao ¹ ^, ² ^, ³ ^, ⁴ , Songli Li ¹ ^, ² ^, ³ ^, ⁴ , Chenqing Wu ¹ ^, ² ^, ³ ^, ⁴ , Jiaqi Wang ¹ ^, ² ^, ³ ^, ⁴ , Nan Zheng ¹ ^, ² ^, ³ ^, ⁴ ^, ^*

Publication date (Electronic): 23 February 2019

Journal: Toxins

Publisher: MDPI

Keywords: aflatoxin M1, ochratoxin A, Caco-2/HT29-MTX co-cultures, mucin, interactive effects

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Abstract

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which widely coexist in milk, may pose a serious threat to human health. Mucin is a major component of the intestinal mucus layer, which plays an important role in maintaining intestinal mucosal homeostasis. However, the effect of mycotoxins AFM1 and OTA on intestinal mucin production is still not clear. This study aimed to investigate individual and interactive effects of mycotoxins AFM1 and OTA on the intestinal barrier and the mRNA expression of intestinal mucin ( MUC2, MUC5AC and MUC5B) and on protein production in Caco-2/HT29-MTX cultures after 48 h of exposure. Our results show that individual mycotoxins and their mixtures significantly reduced intestinal cell viability and transepithelial electrical resistance (TEER) values, as well as significantly altered intestinal mucin mRNA expression and protein abundance. Moreover, OTA showed toxicity similar to AFM1 in cell viability and TEER value at the same concentration. When the two mycotoxins acted in combination, the synergistic effects observed in the assessment of cell viability and protein abundance in all mono- and co-cultures. In general, this study provides evidence that AFM1 and OTA can damage the intestine, and it contributes to optimized maximum permissible limits of mycotoxins in milk.

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Most cited references 46

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Immunological aspects of intestinal mucus and mucins.

Malin Johansson, Gunnar Hansson (2016)

A number of mechanisms ensure that the intestine is protected from pathogens and also against our own intestinal microbiota. The outermost of these is the secreted mucus, which entraps bacteria and prevents their translocation into the tissue. Mucus contains many immunomodulatory molecules and is largely produced by the goblet cells. These cells are highly responsive to the signals they receive from the immune system and are also able to deliver antigens from the lumen to dendritic cells in the lamina propria. In this Review, we will give a basic overview of mucus, mucins and goblet cells, and explain how each of these contributes to immune regulation in the intestine.

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Respiratory tract mucin genes and mucin glycoproteins in health and disease.

Mary Rose, Judith A Voynow (2006)

This review focuses on the role and regulation of mucin glycoproteins (mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (> or =50% carbohydrate, wt/wt). MUC protein backbones are characterized by numerous tandem repeats that contain proline and are high in serine and/or threonine residues, the sites of O-glycosylation. Secretory and membrane-tethered mucins contribute to mucociliary defense, an innate immune defense system that protects the airways against pathogens and environmental toxins. Inflammatory/immune response mediators and the overproduction of mucus characterize chronic airway diseases: asthma, chronic obstructive pulmonary diseases (COPD), or cystic fibrosis (CF). Specific inflammatory/immune response mediators can activate mucin gene regulation and airway remodeling, including goblet cell hyperplasia (GCH). These processes sustain airway mucin overproduction and contribute to airway obstruction by mucus and therefore to the high morbidity and mortality associated with these diseases. Importantly, mucin overproduction and GCH, although linked, are not synonymous and may follow from different signaling and gene regulatory pathways. In section i, structure, expression, and localization of the 18 human MUC genes and MUC gene products having tandem repeat domains and the specificity and application of MUC-specific antibodies that identify mucin gene products in airway tissues, cells, and secretions are overviewed. Mucin overproduction in chronic airway diseases and secretory cell metaplasia in animal model systems are reviewed in section ii and addressed in disease-specific subsections on asthma, COPD, and CF. Information on regulation of mucin genes by inflammatory/immune response mediators is summarized in section iii. In section iv, deficiencies in understanding the functional roles of mucins at the molecular level are identified as areas for further investigations that will impact on airway health and disease. The underlying premise is that understanding the pathways and processes that lead to mucus overproduction in specific airway diseases will allow circumvention or amelioration of these processes.

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Variation and Genetic Control of Protein Abundance in Humans

Linfeng Wu, Sophie Candille, Yoonha Choi … (2013)

Gene expression differs among both individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analyzed extensively in human populations 1–5 , our knowledge is limited regarding the differences in human protein abundance and their genetic basis. Variation in mRNA expression is not a perfect surrogate for protein expression because the latter is influenced by a battery of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest 6,7 . Here we used isobaric tandem mass tag (TMT)-based quantitative mass spectrometry to determine relative protein levels of 5953 genes in lymphoblastoid cell lines (LCLs) from 95 diverse individuals genotyped in the HapMap Project 8,9 . We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations, and sexes. Levels of specific sets of proteins involved in the same biological process co-vary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high throughput human proteome quantification which, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

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Author and article information

Journal

Journal ID (nlm-ta): Toxins (Basel)

Journal ID (iso-abbrev): Toxins (Basel)

Journal ID (publisher-id): toxins

Title: Toxins

Publisher: MDPI

ISSN (Electronic): 2072-6651

Publication date (Electronic): 23 February 2019

Publication date Collection: February 2019

Volume: 11

Issue: 2

Electronic Location Identifier: 132

Affiliations

[1 ]Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; 15501852343@ 123456163.com (X.H.); gyn758521@ 123456126.com (Y.G.); Lisongli@ 123456caas.cn (S.L.); wuchenqing111@ 123456163.com (C.W.); wangjiaqi@ 123456caas.cn (J.W.)

[2 ]Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

[3 ]Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

[4 ]State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Author notes

[* ]Correspondence: zhengnan@ 123456caas.cn ; Tel.: +86-010-6281-6069

[†]

These authors contributed equally to the work.

Article

Publisher ID: toxins-11-00132

DOI: 10.3390/toxins11020132

PMC ID: 6409803

PubMed ID: 30813459

SO-VID: c5066b27-2153-447b-93f5-bb83ae51b8dd

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Modulation of Mucin ( MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A

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Abstract

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Bacterial extracellular vesicles

Most cited references 46

Immunological aspects of intestinal mucus and mucins.

Respiratory tract mucin genes and mucin glycoproteins in health and disease.

Variation and Genetic Control of Protein Abundance in Humans

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