Dataset Information

Bile acids increase intestinal marker expression via the FXR/SNAI2/miR-1 axis in the stomach.

ABSTRACT:

Purpose

Intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Previously, miR-1 has been shown to play an essential role in the initiation of bile acid (BA)-induced IM. The objective of the present study was to investigate the mechanism underlying miR-1 inhibition by BA in gastric cells.

Methods

Ingenuity pathway analysis (IPA) was used to identify molecules acting upstream of miR-1. The effects of deoxycholic acid (DCA), FXR and SNAI2 on the expression of intestinal markers were assessed using quantitative real-time PCR (qRT-PCR) and Western blotting. The expression level of major molecules was detected by immunohistochemistry (IHC) in tissue microarrays. The transcriptional regulation of miR-1 was verified using luciferase reporter and chromatin immunoprecipitation (ChIP) assays.

Results

We found that BA treatment caused aberrant expression of FXR and intestinal markers in gastric cells. Augmented FXR led to transcriptional activation of SNAI2, which in turn suppressed the miR-1 promoter. Moreover, we found that compared with normal tissues, the expression levels of both FXR and SNAI2 were increased and positively correlated with each other in IM tissues. Additionally, their expression showed an inverse correlation with that of miR-1 in IM tissues.

Conclusions

Our findings indicate that FXR may be responsible for a series of molecular changes in gastric cells after BA treatment, and that the FXR/SNAI2/miR-1 axis exhibits a crucial role in BA-induced progression of IM. Blocking the FXR-oriented axis may provide a promising approach for IM or even GC treatment.

SUBMITTER: Wang N

PROVIDER: S-EPMC8516775 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bile acids increase intestinal marker expression via the FXR/SNAI2/miR-1 axis in the stomach.

Wang Na N Wu Siran S Zhao Jing J Chen Min M Zeng Jiaoxia J Lu Guofang G Wang Jiaojiao J Zhang Jian J Liu Junye J Shi Yongquan Y

Cellular oncology (Dordrecht, Netherlands) 20210912 5

<h4>Purpose</h4>Intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Previously, miR-1 has been shown to play an essential role in the initiation of bile acid (BA)-induced IM. The objective of the present study was to investigate the mechanism underlying miR-1 inhibition by BA in gastric cells.<h4>Methods</h4>Ingenuity pathway analysis (IPA) was used to identify molecules acting upstream of miR-1. The effects of deoxycholic ac ...[more]

PMID: 34510400

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Project description:It is a common practice to provide fast-growing broilers with high-fat diets in the context of integrated farms in Northeast China. Therefore, fat digestion, absorption, and utilization efficiency are critical for broiler meat production. Bile acids (BA) promote fat digestion and absorption, but whether and how BA affects muscle growth in broilers remains unclear. In this study, 1-day-old broilers were fed diets containing varying levels of crude fat (low, medium, and high) with or without BA supplementation for 42 d. Chickens fed a high-fat diet supplemented with BA exhibited significantly (P < 0.05) higher body weight (BW) at 21 d and average daily gain (ADG) during the first 21 d compared to the other groups. Throughout the entire experiment, feed conversion rate (FCR) was significantly (P < 0.05) lower in the high-fat group without the addition of BA, which was further decreased (P < 0.05) with BA supplementation. The improved growth performance in the BA-supplemented high-fat group was associated with significantly (P < 0.05) higher lipase activity in the small intestine chyme, a decreased trend (P = 0.06) in abdominal fat ratio, and significantly (P < 0.05) higher breast muscle mass. Histological analysis revealed significant (P < 0.05) increases in myofiber diameter, cross-sectional area, and RNA and DNA concentrations in the breast muscle of BA-supplemented broilers on the high-fat diet. Additional histological analysis further revealed significant (P < 0.05) enhancements in myofiber diameter, cross-sectional area, and RNA and DNA concentrations within the breast muscles of broilers supplemented with BA and a high-fat diet. The increased insulin-like growth factor 2 (IGF2) in the breast muscle of broilers fed a BA-supplemented high-fat diet correlated with significantly (P < 0.05) increased farnesoid X factor (FXR) protein expression and binding to the IGF2 promoter. These results suggest that dietary BA supplementation improves FCR and breast muscle growth in broilers fed a high-fat diet, potentially through the FXR-mediated IGF2 pathway.

Dataset Information

Bile acids increase intestinal marker expression via the FXR/SNAI2/miR-1 axis in the stomach.

Purpose

Methods

Results

Conclusions

Publications

Bile acids increase intestinal marker expression via the FXR/SNAI2/miR-1 axis in the stomach.

Similar Datasets

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