Sa Xiao1, Qiuping Li1, Kun Hu1, Yu He1, Qing Ai1, Liuhong Hu2, Jialin Yu3. 1. Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China; Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China. 2. Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China; Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Pediatrics, Shenzhen University General Hospital, Shenzhen, China. 3. Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China; Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Department of Pediatrics, Shenzhen University General Hospital, Shenzhen, China. Electronic address: yujialin486@126.com.
Abstract
BACKGROUND: Exaggerated inflammation that characterizes necrotizing enterocolitis (NEC) is caused by the invasion of pathogens through an immature intestinal barrier. Vitamin A (VA) and retinoic acid (RA) play important roles in the growth of epithelial tissue and in modulating immune function. OBJECTIVE: To investigate the roles of VA and RA in the development of NEC. METHODS: Levels of serum retinol in patients and in a NEC mouse model were detected with high-performance liquid chromatography. Bacterial communities of NEC mice treated with VA or PBS were detected by high-throughput sequencing. In vitro and in vivo, levels of inflammatory factors were measured by ELISA and RT-PCR, and expression levels of claudin-1, occludin, and ZO-1 were detected by Western blotting. Transepithelial electrical resistance (TEER) was measured in Caco-2 cell monolayers. RESULTS: The level of VA in the NEC patients was lower than in the control patients. In the NEC mice that were treated with VA versus PBS, the proportion of Escherichia-Shigella was lower, while the abundance of Bacteroides was markedly higher. Both in vivo and in vitro, the levels of inflammatory factors were significantly reduced, while the expression levels of claudin-1, occludin, and ZO-1 were increased, after the VA and RA treatments. Meanwhile, TEER was increased and lipopolysaccharide-induced damage was reduced in Caco-2 cell monolayers after RA treatment. CONCLUSIONS: These results suggest that VA may regulate intestinal flora, alleviate inflammatory reactions, and enhance the intestinal epithelial barrier in NEC. Thus, VA may be an effective drug for providing protection against NEC in newborns.
BACKGROUND: Exaggerated inflammation that characterizes necrotizing enterocolitis (NEC) is caused by the invasion of pathogens through an immature intestinal barrier. Vitamin A (VA) and retinoic acid (RA) play important roles in the growth of epithelial tissue and in modulating immune function. OBJECTIVE: To investigate the roles of VA and RA in the development of NEC. METHODS: Levels of serum retinol in patients and in a NEC mouse model were detected with high-performance liquid chromatography. Bacterial communities of NEC mice treated with VA or PBS were detected by high-throughput sequencing. In vitro and in vivo, levels of inflammatory factors were measured by ELISA and RT-PCR, and expression levels of claudin-1, occludin, and ZO-1 were detected by Western blotting. Transepithelial electrical resistance (TEER) was measured in Caco-2 cell monolayers. RESULTS: The level of VA in the NEC patients was lower than in the control patients. In the NEC mice that were treated with VA versus PBS, the proportion of Escherichia-Shigella was lower, while the abundance of Bacteroides was markedly higher. Both in vivo and in vitro, the levels of inflammatory factors were significantly reduced, while the expression levels of claudin-1, occludin, and ZO-1 were increased, after the VA and RA treatments. Meanwhile, TEER was increased and lipopolysaccharide-induced damage was reduced in Caco-2 cell monolayers after RA treatment. CONCLUSIONS: These results suggest that VA may regulate intestinal flora, alleviate inflammatory reactions, and enhance the intestinal epithelial barrier in NEC. Thus, VA may be an effective drug for providing protection against NEC in newborns.
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