肠上皮
肠粘膜
潘尼斯电池
基因沉默
生物
细胞凋亡
溃疡性结肠炎
结肠炎
LGR5型
势垒函数
平衡
上皮
免疫学
癌症研究
细胞生物学
小肠
分子生物学
内科学
医学
内分泌学
Wnt信号通路
疾病
信号转导
基因
生物化学
遗传学
作者
Tina Yu,Sudhakar Kalakonda,Xiangzheng Liu,Naomi Han,Hee Kyoung Chung,Lan Xiao,Rao N. Jaladanki,Tong‐Chuan He,Jean‐Pierre Raufman,Jian‐Ying Wang
标识
DOI:10.1096/fasebj.2022.36.s1.0r837
摘要
The mammalian intestinal epithelium is colonized by complex microbiota and exposed to a wide variety of luminal noxious substances. Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in gut pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function.Intestinal mucosal tissues were collected from mice following dextran sodium sulfate (DSS) treatment or fasting, and from patients with ulcerative colitis and Crohn's disease. We isolated primary enterocytes from the small intestine of mice and developed intestinal organoids. Levels of uc.230 were silenced in intestinal epithelial cells (IECs) and organoids by transfection with small interfering RNAs or elevated using a plasmid vector that overexpressed uc.230. Association of uc.230 with miR-503 was determined by biotinylated RNA pulldown assays.Compared with controls, intestinal mucosal tissues from mice with DSS-induced colitis or fasted for 48 h and from patients with ulcerative colitis had increased levels of uc.230. The uc.230 content in Crohn's disease tissues was the same as in control tissue. Silencing uc.230 inhibited the growth of IECs and intestinal organoids and resulted in epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptotic cell death, whereas increasing uc.230 levels protected IECs against apoptosis. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation.Our results indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and protects IECs against apoptosis at least in part by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.
科研通智能强力驱动
Strongly Powered by AbleSci AI