通过B3GNT8介导的糖化维持肠道平衡,并保护大肠炎
Haoyun Mao1, Yi Cao1, Ying Lu2
1Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
像B3GNT8这样的β1,3-N-乙糖氨基基转移酶 (B3GNTs) 对肠道健康至关重要. 降低B3GNT8水平会恶化肠道炎症和易患炎症性肠病 (IBD).
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠道糖化变化与炎症性肠病 (IBD) 病原发生有关.
- 肠道糖化在维持肠道平衡中的确切作用尚未完全理解.
- β1,3-N-乙烯基葡萄糖胺基转移酶 (B3GNTs) 合成聚N-乙烯基乳糖胺链,影响细胞功能.
研究的目的:
- 使用淘汰赛小鼠模型研究B3GNT8对肠道平衡的特定影响.
- 确定B3GNT8表达与炎症性肠病 (IBD) 进展,特别是性结肠炎 (UC) 之间的相关性.
主要方法:
- 产生B3gnt8淘汰赛 (B3gnt8-/-) 的小鼠.
- 在IBD患者粘膜中分析B3GNT8mRNA和蛋白质水平.
- 在B3gnt8-/-小鼠中评估DSS诱导的肠炎症.
- 评估紧密结合完整性,粘素分泌,帕内斯细胞种群,溶酶含量,细菌组成和溶酶稳定性.
主要成果:
- 在炎症IBD粘膜中,B3GNT8mRNA和蛋白质水平显著降低,与UC严重程度负相关.
- B3gnt8-/-小鼠对DSS诱导的大肠炎的敏感性增加,紧接口受损,粘素分泌受损.
- B3gnt8的损失导致帕内斯细胞数量的减少,酶的减少,肠道微生物群的改变,以及 lysosomal 稳定性的损害.
- B3GNT8缺乏会通过ATG16L1-ATG12-ATG5通路扰乱帕内斯细胞的自-溶酶体通路.
结论:
- B3GNT8通过其对糖化,帕内斯细胞功能和自-溶解体通路的影响,在维持肠道平衡中发挥着至关重要的作用.
- 减少B3GNT8表达与对肠道炎症和IBD的敏感性增加有关.
- B3GNT8代表了新型IBD治疗的潜在治疗标.
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