Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Neurogastroenterol Motil. 2021 Jan;33(1):e13955. doi: 10.1111/nmo.13955. Epub 2020 Aug 9.
There is increased recognition of duodenal disturbances (inflammation, altered mucosal protein expression, and chemosensitivity) in functional dyspepsia (FD). Besides sensorimotor functions, enteric submucosal neurons also regulate epithelial ion transport. We hypothesized that duodenal mucosal ion transport and expression of associated genes are altered in FD.
Duodenal mucosal ion transport (basal and acetylcholine- and glucose-evoked changes in short-circuit current [Isc]) and expression of associated genes and regulatory miRNAs were evaluated in 40 FD patients and 24 healthy controls.
Basal Isc (FD: 88.2 [52.6] μA/cm vs healthy: 20.3 [50.2] μA/cm ; P ≤ .0001), acetylcholine-evoked Isc (FD: Emax 50.4 [35.8] μA/cm vs healthy: 16.6 [15] μA/cm ; P ≤ .001), and glucose-evoked Isc responses (FD: E 69.8 [42.1] μA/cm vs healthy: 40.3 [24.6] μA/cm ; P = .02) were greater in FD than in controls. The Emax for glucose was greater in FD patients on selective serotonin reuptake inhibitors. In FD, the mRNA expression of SLC4A7 and SLC4A4, which transport bicarbonate into cells at the basolateral surface, and the apical anion exchanger SLC26A3 were reduced (false discovery rate <0.05), the serotonin receptor HTR4 was increased, and the serotonin transporter SLC6A4 was decreased. Selected miRNAs (hsa-miR-590-3p, hsa-miR-32-5p) that target genes associated with ionic transport were upregulated in FD.
Compared to controls, FD patients had greater baseline and agonist-evoked duodenal mucosal secretory responses. These findings may be explained by reduced gene expression, which would be anticipated to reduce luminal bicarbonate secretion. The upregulated miRNAs may partly explain the downregulation of these genes in FD.
功能性消化不良（FD）患者中十二指肠功能紊乱（炎症、粘膜蛋白表达改变和化学敏感性）的认识不断提高。除了感觉运动功能外，肠粘膜下神经元还调节上皮细胞离子转运。我们假设 FD 患者的十二指肠粘膜离子转运和相关基因的表达发生改变。
评估 40 例 FD 患者和 24 例健康对照者的十二指肠粘膜离子转运（基础和乙酰胆碱及葡萄糖诱发的短路电流[Isc]变化）及相关基因和调节 miRNA 的表达。
FD 患者基础 Isc（FD：88.2 [52.6] μA/cm 比健康对照：20.3 [50.2] μA/cm；P ≤ 0.0001）、乙酰胆碱诱发的 Isc（FD：Emax 50.4 [35.8] μA/cm 比健康对照：16.6 [15] μA/cm；P ≤ 0.001）和葡萄糖诱发的 Isc 反应（FD：E 69.8 [42.1] μA/cm 比健康对照：40.3 [24.6] μA/cm；P = 0.02）均高于对照组。服用选择性 5-羟色胺再摄取抑制剂的 FD 患者葡萄糖的 Emax 更高。FD 患者 SLC4A7 和 SLC4A4 的 mRNA 表达（将碳酸氢盐转运到基底外侧表面的细胞内）和顶端阴离子交换 SLC26A3 减少（错误发现率<0.05），5-羟色胺受体 HTR4 增加，5-羟色胺转运体 SLC6A4 减少。与离子转运相关的基因的选定 miRNA（hsa-miR-590-3p、hsa-miR-32-5p）在 FD 中上调。
与对照组相比，FD 患者的十二指肠粘膜基础和激动剂诱发的分泌反应更大。这些发现可以用基因表达减少来解释，预计这会减少管腔碳酸氢盐分泌。上调的 miRNA 可能部分解释了 FD 中这些基因的下调。
