miRNA-regulated gene expression differs in celiac disease patients according to the age of presentation
miRNA-regulated gene expression differs in celiac disease patients according to the age of presentation
复制标题
DOI：
10.1007/s12263-015-0482-2
复制
发表时间：
2015-09-01
影响因子：
3.5
通讯作者：
Barisani, Donatella
中科院分区：
文献类型：
--
作者：
Comani, Gaia Buoli;Panceri, Roberto;Barisani, Donatella
乳糜泻是一种肠道疾病，在儿童和成人患者中表现出不同的症状和临床表现。这些变化可能归因于年龄相关的肠道结构和肠道免疫系统的变化，其特征在于可能由miRNA调控的基因表达差异。我们分析了Marsh 3AB和3C型小儿乳糜泻患者与对照组十二指肠活检中的一组miRNAs及其靶基因。此外，为了评估血浆样品中表达的变化，我们评估了对照组和诊断时或无麸质饮食的患者的循环miRNA水平。我们在乳糜泻患者中检测到miR192 - 5p表达降低，但NOD2和CXCL2（先前在成人中鉴定的靶点）没有变化。相反，我们检测到另一个靶点MAD2L1的mRNA和蛋白质水平显著增加，MAD2L1是与细胞周期控制相关的蛋白质。miR-31 - 5p和miR-338 - 3p下调，其各自的靶点FOXP3和RUNX1参与Treg功能，在乳糜泻患者中上调。最后，我们在乳糜泻患者中检测到miR-21 - 5 p的表达增加，这可能是由其推定靶点STAT 3的调节环引起的，这表明Marsh 3C患者的激活增加。血浆分析显示了与活检中观察到的趋势相似的趋势，但在无麸质饮食的存在下，我们无法检测到与对照相当的循环miRNA值。miRNAs及其靶基因在乳糜泻患儿十二指肠黏膜和血浆中的表达发生改变，这些改变可能与成人不同。
Celiac disease is an intestinal disease which shows different symptoms and clinical manifestations among pediatric and adult patients. These variations could be imputable to age-related changes in gut architecture and intestinal immune system, which could be characterized by gene expression differences possibly regulated by miRNAs. We analyzed a panel of miRNAs and their target genes in duodenal biopsies of Marsh 3AB and 3C pediatric celiac patients, compared to controls. Moreover, to assess variation of expression in plasma samples, we evaluated circulating miRNA levels in controls and patients at diagnosis or on gluten-free diet. We detected a decreased miR192-5p expression in celiac patients, but no variations in NOD2 and CXCL2, targets previously identified in adults. Conversely, we detected a significant increase in mRNA and protein levels of another target, MAD2L1, protein related to cell cycle control. miR-31-5p and miR-338-3p were down-regulated and their respective targets, FOXP3 and RUNX1, involved in Treg function, resulted up-regulated in celiac patients. Finally, we detected, in celiac patients, an increased expression of miR-21-5p, possibly caused by a regulatory loop with its putative target STAT3, which showed an increased activation in Marsh 3C patients. The analysis of plasma revealed a trend similar to that observed in biopsies, but in presence of gluten-free diet we could not detect circulating miRNAs values comparable to controls. miRNAs and their gene targets showed an altered expression in duodenal mucosa and plasma of celiac disease pediatric patients, and these alterations could be different from adult ones.