Dataset Information

Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

ABSTRACT: Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof's potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.

SUBMITTER: Canter JA

PROVIDER: S-EPMC8508755 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

Canter Jessica A JA Ernst Sarah E SE Peters Kristin M KM Carlson Bradley A BA Thielman Noelle R J NRJ Grysczyk Lara L Udofe Precious P Yu Yunkai Y Cao Liang L Davis Cindy D CD Gladyshev Vadim N VN Hatfield Dolph L DL Tsuji Petra A PA

International journal of molecular sciences 20210930 19

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (<i>Selenof</i>) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of <i>Selenof</i> on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post- ...[more]

PMID: 34638991

Similar Datasets

Project description:Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

Project description:Bacillus licheniformis (B. Licheniformis) has been considered to be an effective probiotic to maintain gut health and boost productivity in the pig industry, but there is no complete understanding of its mechanisms. We determined whether weaned piglets exposed to BL-S6 (probiotic) had altered intestinal barrier function or microbiota composition. In our study, 108 weaned piglets (54 barrows and 54 gilts) were divided equally into three groups, each with six pens and six piglets/pen, and fed a basal diet supplemented without or with antibiotic (40 g/t of Virginiamycin and 500 g/t of Chlortetracycline) or probiotic (1000 g/t of B. Licheniformis) for a 14-day trial. On day 14, one piglet was chosen from each pen to collect blood and intestinal samples. Compared with the control group, dietary supplementation with a probiotic promoted body weight (BW) gain and average daily gains (ADG) while reducing diarrhea incidence (p < 0.05). Probiotics enhanced superoxidase dismutase (SOD) activity and decreased malondialdehyde (MDA) levels in serum (p < 0.05), and increased the level of mRNA expression of SOD1, Nrf2, and HO-1 (p < 0.05) in the jejunum mucosa. Moreover, supplementation with probiotics improved intestinal mucosal integrity as evidenced by higher villus heights and a higher ratio of villus heights to crypt depths (duodenum and jejunum) and higher mRNA and protein levels of occludin and ZO-1 in jejunum mucosa (p < 0.05). The intestinal sIgA levels (p < 0.05) were elevated in the probiotic group, and that of serum immunoglobulin A (IgA) tended to be higher (p = 0.09). Furthermore, weaning piglets who were given probiotics had a better balance of the cecum microbiota, with lactobacillus abundance increased and clostridium_sensu_stricto_1 abundance decreased. In conclusion, dietary supplementation with the probiotic BL-S6 promoted intestinal integrity, which was associated, in part, with modulating intestinal barrier function and microbial diversity in weaned piglets; it may offer a promising alternative to antibiotics to prevent diarrhea.

Dataset Information

Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

Publications

Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets