脱氧胆酸
微泡
肠化生
CDX2
基因沉默
生物
小RNA
化生
分子生物学
癌症研究
化学
胆汁酸
转录因子
内科学
生物化学
医学
胃
同源盒
基因
作者
Xiaoquan Xu,Jinnian Cheng,Shengzheng Luo,Dan Huang,Jingxian Xu,Yueqin Qian,Hui Zhou,Xinjian Wan
标识
DOI:10.1016/j.ejphar.2020.173566
摘要
The crosstalk between macrophages and gastric epithelial cells has emerged as a player in chronic inflammation during intestinal metaplasia. However, the role of bile acid on this modulation remains to be studied. We hypothesized that deoxycholic acid-induced macrophages secreted exosomes to mediate intercellular communication and promoted intestinal metaplasia in human gastric epithelial cells (GES-1 cells). Macrophage-derived exosomes (M-Exos) and deoxycholic acid-induced macrophage-derived exosomes (D-Exos) were isolated by ultracentrifugation. EdU staining and CCK-8 assay were utilized to evaluate the effects of exosomes on the proliferation of GES-1 cells. Intestinal metaplasia was assessed by the expression of caudal-related homeobox transcription factor 2 (CDX2) at both mRNA and protein level. MicroRNA sequencing revealed the microRNA (miRNA) expression profiles of M-Exos and D-Exos. The role of a specific miRNA and mRNA was analyzed by using miRNA mimics, miRNA inhibitors and siRNAs. D-Exos promoted the expression of CDX2 and suppressed the proliferation of GES-1 cells, compared to M-Exos. The miRNA profiles and quantitative real-time PCR examination showed D-Exos enriched a higher level of hsa-miR-30a-5p than M-Exos. Overexpressed has-miR-30a-5p increased CDX2 expression and inhibited the proliferation in GES-1 cells via targeted Forkhead Box D1 (FOXD1), a potential regulatory factor in the process of intestinal metaplasia. D-Exos may promote intestinal metaplasia and suppress proliferation of GES-1 cells via hsa-miR-30a-5p targeting FOXD1, which may be involved in the action mechanism of bile acid on gastric mucosa.
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