Jinwei Sun1, Wenxing Liang1, Xiaofeng Yang1, Qiming Li1, Guofang Zhang2. 1. Product Research and Development Center, Newhopedairy Co., Ltd, Chengdu 610011, Sichuan, China. 2. Key Laboratory of Dairy Science, College of Food Science, Northeast Agricutural University, Harbin 150030, Heilongjiang, China. Electronic address: s24512453@126.com.
Abstract
AIMS: Despite the protective effect of galacto-oligosaccharides (GOS) on human colon has been widely-reported, the mechanism of its beneficial effect is still unclear. This paper aims to reveal the internal mechanism underlined the anti-colitis effect of GOS by studying its regulatory effect on miRNAs. MAIN METHODS: An in vitro model of colitis was constructed by using human colon epithelial FHC cells and lipopolysaccharide (LPS). An in vivo colitis model was established as well, by injecting Rag2-/- Sprague-Dawley (SD) rats with helicobacter hepaticus. The effects of GOS pre-treatment on these two models were tested, and the miRNAs involved in these effects were studied. KEY FINDINGS: The expression of miR-19b, miR-590-5p and miR-495 was up-regulated, and the expression of miR-29a, miR-31 and miR-142-5p was down-regulated by GOS treatment in both normal and LPS-stimulated FHC cells. Among which, miR-19b was the most varied miRNA. GOS pre-treatment significantly attenuated LPS-induced cell injury, as evidenced by the increase of cell viability, the decrease of apoptosis, as well as the suppressed release of TNF-α, IFN-γ and IL-1β. GOS pre-treatment could also prevent Rag2-/- rats against helicobacter hepaticus injection induced diarrhea and inflammation, as the body weight and colon organ weight were recovered, diarrhea score was declined, and the release of pro-inflammatory cytokines was inhibited. The in vitro and in vivo effects of GOS abovementioned were all impeded when miR-19b was silenced. SIGNIFICANCE: In vitro and in vivo experiments showed that GOS have certain anti-colitis effect, and this effect may be achieved by up-regulating miR-19b.
AIMS: Despite the protective effect of galacto-oligosaccharides (GOS) on human colon has been widely-reported, the mechanism of its beneficial effect is still unclear. This paper aims to reveal the internal mechanism underlined the anti-colitis effect of GOS by studying its regulatory effect on miRNAs. MAIN METHODS: An in vitro model of colitis was constructed by using humancolon epithelial FHC cells and lipopolysaccharide (LPS). An in vivo colitis model was established as well, by injecting Rag2-/- Sprague-Dawley (SD) rats with helicobacter hepaticus. The effects of GOS pre-treatment on these two models were tested, and the miRNAs involved in these effects were studied. KEY FINDINGS: The expression of miR-19b, miR-590-5p and miR-495 was up-regulated, and the expression of miR-29a, miR-31 and miR-142-5p was down-regulated by GOS treatment in both normal and LPS-stimulated FHC cells. Among which, miR-19b was the most varied miRNA. GOS pre-treatment significantly attenuated LPS-induced cell injury, as evidenced by the increase of cell viability, the decrease of apoptosis, as well as the suppressed release of TNF-α, IFN-γ and IL-1β. GOS pre-treatment could also prevent Rag2-/- rats against helicobacter hepaticus injection induced diarrhea and inflammation, as the body weight and colon organ weight were recovered, diarrhea score was declined, and the release of pro-inflammatory cytokines was inhibited. The in vitro and in vivo effects of GOS abovementioned were all impeded when miR-19b was silenced. SIGNIFICANCE: In vitro and in vivo experiments showed that GOS have certain anti-colitis effect, and this effect may be achieved by up-regulating miR-19b.
Authors: Takahiko Toyonaga; Erin C Steinbach; Benjamin P Keith; Jasmine B Barrow; Matthew R Schaner; Elisabeth A Wolber; Caroline Beasley; Jennifer Huling; Yuli Wang; Nancy L Allbritton; Nicole Chaumont; Timothy S Sadiq; Mark J Koruda; Animesh Jain; Millie D Long; Edward L Barnes; Hans H Herfarth; Kim L Isaacs; Jonathan J Hansen; Michael T Shanahan; Reza Rahbar; Terrence S Furey; Praveen Sethupathy; Shehzad Z Sheikh Journal: Cell Mol Gastroenterol Hepatol Date: 2020-06-16