Down-regulation of monocarboxylate transporter 1 (<i>MCT1</i>) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

Tudela, Carmen Villodre; Boudry, Christelle; Stumpff, Friederike; Aschenbach, Jörg R.; Vahjen, Wilfried; Zentek, Jürgen; Pieper, Robert

doi:10.1017/s0007114514004231

Cited by 86 publications

(50 citation statements)

References 37 publications

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“…In Caco-2 cells, treatment with the proinflammatory cytokine TNF-α decreases the expression of MCT1, suggesting that inflammation might be associated with suppression of MCT1 expression (130). In pigs as an animal model, high-protein diet leads to bacterial fermentation of proteins in the colon, resulting in increased production of TNF-α, and this condition is also associated with decreased expression of MCT1 (130).…”

Section: Proton-coupled Transporters For Scfamentioning

confidence: 99%

Short‐Chain Fatty Acid Transporters: Role in Colonic Homeostasis

Sivaprakasam

Bhutia

Yang

et al. 2017

Comprehensive Physiology

189

117

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Short-chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated in colon by bacterial fermentation of dietary fiber. Though diffusion in protonated form is a significant route, carrier-mediated mechanisms constitute the major route for the entry of SCFA in their anionic form into colonic epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1 (SLC16A1) and MCT4 (SLC16A3) are H+-coupled and mediate electroneutral transport of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+-coupled; SMCT1-mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas SMCT2-mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1 and SMCT2 are expressed exclusively in the apical membrane. An anion-exchange mechanism also operates in the apical membrane in which SCFA entry in anionic form is coupled to bicarbonate efflux; the molecular identity of this exchanger however remains unknown. All these transporters are subject to regulation, notably by their substrates themselves; this process involves cell-surface receptors with SCFA as signaling molecules. There are significant alterations in the expression of these transporters in ulcerative colitis and colon cancer. The tumor-associated changes occur via transcriptional regulation by p53 and HIF1α and by promoter methylation. As SCFA are obligatory for optimal colonic health, the transporters responsible for the entry and transcellular transfer of these bacterial products in colonic epithelium are critical determinants of colonic function under physiological conditions and in disease states.

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Section: Proton-coupled Transporters For Scfamentioning

confidence: 99%

Short‐Chain Fatty Acid Transporters: Role in Colonic Homeostasis

Sivaprakasam

Bhutia

Yang

et al. 2017

Comprehensive Physiology

189

117

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“…Butyrate is a beneficial metabolite mostly produced by the microbiota from indigestible carbohydrates for which transport is deficient in IBD [49]. Moreover, an HP diet decreased the mucosal expression of the butyrate transporter monocarboxylate transporter 1 (MCT1) in pigs [50], but this effect was not observed in rats [22] in different experimental conditions. Then, the impacts of the HP diet described above on the microbiota and colonic epithelium might be amplified in individuals with a compromised barrier function, explaining this increased risk of relapse associated with an HP intake in IBD patients [42].…”

Section: Potential Role Of Dietary Proteins In Inflammatory Flarementioning

confidence: 99%

“…The AA-derived microbial metabolites phenol and ammonia have been found to increase epithelial permeability [74], while indole and branched-chain fatty acids have shown protective effects on this intestinal parameter [75,76,77]. Among AA-derived bacterial metabolites, ammonia and H 2 S have been shown to induce the expression of pro-inflammatory genes in colonic IEC [50,65] while indole and related compounds exert immuno-regulatory effects [75,76,78,79]. Recently, the bacterial AA-degradation products histamine and spermine have been shown to regulate inflammation in the intestinal epithelium [80].…”

Section: Potential Role Of Dietary Proteins In Inflammatory Flarementioning

confidence: 99%

Dietary Protein and Amino Acid Supplementation in Inflammatory Bowel Disease Course: What Impact on the Colonic Mucosa?

et al. 2017

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Inflammatory bowel diseases (IBD), after disease onset, typically progress in two cyclically repeated phases, namely inflammatory flare and remission, with possible nutritional status impairment. Some evidence, either from epidemiological, clinical, and experimental studies indicate that the quantity and the quality of dietary protein consumption and amino acid supplementation may differently influence the IBD course according to the disease phases. For instance, although the dietary protein needs for mucosal healing after an inflammatory episode remain undetermined, there is evidence that amino acids derived from dietary proteins display beneficial effects on this process, serving as building blocks for macromolecule synthesis in the wounded mucosal area, energy substrates, and/or precursors of bioactive metabolites. However, an excessive amount of dietary proteins may result in an increased intestinal production of potentially deleterious bacterial metabolites. This could possibly affect epithelial repair as several of these bacterial metabolites are known to inhibit colonic epithelial cell respiration, cell proliferation, and/or to affect barrier function. In this review, we present the available evidence about the impact of the amount of dietary proteins and supplementary amino acids on IBD onset and progression, with a focus on the effects reported in the colon.

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“…We demonstrated here that PoCo83-3 cells expressed the mRNA transcripts of genes coding for the transport proteins ENaC, DRA, CFTR, and MCT1 ( Fig. 6 ), which have been proposed to mediate transcellular transport processes in the colon [Ritzhaupt et al, 1998;Kunzelmann and Mall, 2002;Musch et al, 2009;Talbot and Lytle, 2010;Villodre Tudela et al, 2015]. Thus, we expect PoCo83-3 to provide new perspectives in transport physiological studies.…”

Section: Poco83-3 Characteristics Resemble Those Of Colonic Epitheliamentioning

confidence: 71%

Establishment and Characterization of an SV40 Large T Antigen-Transduced Porcine Colonic Epithelial Cell Line

Kaiser

Böttner²,

Wedel³

et al. 2017

Cells Tissues Organs

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Continuous cell lines have become indispensable tools that have enabled investigations into cellular mechanisms by increasing experimental reproducibility and sample availability, and decreasing the use of experimental animals. To facilitate studies of epithelial barrier function of the porcine colon, we aimed to establish an epithelial cell line with an extended replicative capacity. Cells were isolated from the proximal colon of a 3-week-old piglet and transduced using a recombinant retroviral vector construct containing the simian virus 40 large T antigen (SV40 TAg). We established a clonal epithelial cell line, referred to as PoCo83-3, that stably expressed the SV40 TAg, verified at mRNA and protein levels. PoCo83-3 showed epithelial cell-specific features, such as cobblestone-like morphology, dome structure formation, the presence of apical microvilli, and the expression of keratin 18, E-cadherin and the tight junction-associated proteins zonula occludens-1, occludin, and claudin-1. To validate PoCo83-3 as an in vitro model in epithelial barrier research, proinflammatory cytokine-inducible alterations in barrier integrity were demonstrated by incubating the cells with TNF-α and IFN-γ for 48 h. These cytokine treatments promoted a decreased transepithelial electrical resistance. In summary, PoCo83-3 exhibited an extended life span and a differentiated phenotype while maintaining epithelial characteristics. Based on these results, we present this cell line as a valuable in vitro model for investigations of epithelial barrier function in the porcine colon.

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Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

Cited by 86 publications

References 37 publications

Short‐Chain Fatty Acid Transporters: Role in Colonic Homeostasis

Short‐Chain Fatty Acid Transporters: Role in Colonic Homeostasis

Dietary Protein and Amino Acid Supplementation in Inflammatory Bowel Disease Course: What Impact on the Colonic Mucosa?

Establishment and Characterization of an SV40 Large T Antigen-Transduced Porcine Colonic Epithelial Cell Line

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