Background. Overexpression of miRNA-211 suppresses the differentiation of bone marrow stem cells into intestinal ganglion cells via downregulation of GDNF, a regulator of intestine barrier function. The study aimed to investigate the interaction between miR-211 and GDNF on intestinal epithelial cells. Methods. The expression levels of miR-211 and GDNF in duodenal biopsy specimens from FD patients and healthy controls were compared. Enteric glia cell (EGCs) cell line transfected with miR-211 mimics and inhibitors were used to clarify the expression levels of GDNF were analyzed by qRT-PCR and ELISA. Intestine epithelial cell (IECs) cell line cultured in medium from ECGs in different transfection conditions were used in wound healing assay, cell proliferation assay, and western blotting for evaluation of p38 MAPK phosphorylation level. Results. MiR-211 expression was significantly upregulated in the duodenal tissue of patients with FD compared to healthy subjects, whereas GDNF expression was significantly downregulated (both ). Transfection with miR-211 mimics significantly decreased GDNF mRNA expression and protein secretion (). An inhibited intestinal epithelial cell wound healing () and increased expression levels of phosphorylated p38 MAPK () were found in IECs cultured with medium from EGCs transfected with miR-211 mimics. Conclusions. MiR-211 may downregulates GDNF mRNA and protein expression via activation of the pp38 MAPK signaling pathway. Targeting miR-211 or the MAPK pathway may be a potential intervention for FD.

中文翻译：

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通过增加 p38 MAPK 通路的磷酸化下调神经胶质细胞系衍生的神经营养因子 (GDNF)，在功能性消化不良中过度表达 microRNA-211

背景。miRNA-211 的过表达通过下调肠屏障功能调节剂 GDNF 来抑制骨髓干细胞向肠神经节细胞的分化。该研究旨在研究 miR-211 和 GDNF 对肠上皮细胞的相互作用。方法. 比较 FD 患者和健康对照的十二指肠活检标本中 miR-211 和 GDNF 的表达水平。用 miR-211 模拟物和抑制剂转染的肠神经胶质细胞 (EGC) 细胞系用于通过 qRT-PCR 和 ELISA 分析 GDNF 的表达水平。在不同转染条件下从 ECGs 在培养基中培养的肠上皮细胞 (IECs) 细胞系用于伤口愈合测定、细胞增殖测定和蛋白质印迹以评估 p38 MAPK 磷酸化水平。结果。与健康受试者相比，FD 患者的十二指肠组织中 MiR-211 表达显着上调，而 GDNF 表达显着下调（两者均). 用 miR-211 模拟物转染显着降低了 GDNF mRNA 表达和蛋白质分泌（). 抑制肠上皮细胞伤口愈合（)和磷酸化 p38 MAPK ()在 IEC 中发现，这些 IEC 是用来自用 miR-211 模拟物转染的 EGC 的培养基培养的。结论。MiR-211 可能通过激活 pp38 MAPK 信号通路下调 GDNF mRNA 和蛋白表达。靶向 miR-211 或 MAPK 通路可能是 FD 的潜在干预措施。