Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, plays an important role in cell-to-cell communication during colitis.
Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, plays an important role in cell-to-cell communication during colitis.
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由肠上皮PEPT1调节的结肠miRNA表达/分泌在结肠炎期间在细胞对细胞通信中起重要作用。
DOI：
10.1371/journal.pone.0087614
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Ayyadurai S;Charania MA;Xiao B;Viennois E;Zhang Y;Merlin D
PepT 1是质子-寡肽协同转运蛋白家族SLC 15的成员，其介导二/三肽从肠腔转运到上皮细胞。microRNAs（miRNAs）是一类长度为21-23个核苷酸的小分子非编码RNA，通过与靶mRNA的3′-非翻译区（UTRs）结合来调节基因的转录后表达。尽管大多数miRNA的作用仍然难以捉摸，但它们已经涉及重要的细胞功能，如肠上皮细胞分化、增殖和凋亡。在本研究中，我们研究了肠上皮PepT 1表达对对照小鼠和实验诱导的结肠炎（结肠炎）小鼠结肠中microRNA（miRNA）表达/分泌的影响。在结肠炎和对照小鼠中，结肠miRNA表达失调，但miRNA表达/分泌失调是结肠组织特异性的，不影响其他组织，如脾脏和肝脏。肠上皮PepT 1依赖性结肠miRNA表达失调不仅影响上皮细胞，还影响其他细胞类型，如肠巨噬细胞。重要的是，我们发现已知与炎症性肠病有关的miRNA 23 b在细胞间分泌和转运，对受体肠道巨噬细胞产生基因沉默作用。基于我们的数据，我们可以得出结论，特定蛋白PepT 1在肠道中的表达以组织特异性方式影响结肠中局部miRNA的表达/分泌，并且可能在结肠炎的诱导和进展过程中发挥重要作用。受肠上皮PepT 1调节的结肠miRNA表达/分泌可能在结肠炎期间的细胞间通讯中起关键作用。
PepT1 is a member of the proton-oligopeptide cotransporter family SLC15, which mediates the transport of di/tripeptides from intestinal lumen into epithelial cells. MicroRNAs (miRNAs), a small noncoding RNAs (21–23 nucleotides), post-transcriptionally regulate gene expression by binding to the 3′-untranslated regions (UTRs) of their target mRNAs. Although the role of most miRNAs remains elusive, they have been implicated in vital cellular functions such as intestinal epithelial cells differentiation, proliferation, and apoptosis. In the present study, we investigated the effect of intestinal epithelial PepT1 expression on microRNA (miRNA) expression/secretion in the colons of control mice and in mice with experimentally induced colonic inflammation (colitis). The colonic miRNA expression was deregulated in both colitis and control mice but the deregulation of miRNA expression/secretion was specific to colonic tissue and did not affect other tissues such as spleen and liver. Intestinal epithelial PepT1-dependent deregulation of colonic miRNA expression not only affects epithelial cells but also other cell types, such as intestinal macrophages. Importantly, we found the miRNA 23b which was known to be involved in inflammatory bowel disease was secreted and transported between cells to impose a gene-silencing effect on recipient intestinal macrophages. Based on our data, we may conclude that the expression of a specific protein, PepT1, in the intestine affects local miRNA expression/secretion in the colon on a tissue specific manner and may play an important role during the induction and progression of colitis. Colonic miRNA expression/secretion, regulated by intestinal epithelial PepT1, could play a crucial role in cell-to-cell communication during colitis.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
29.4
作者：
Dalmasso G;Nguyen HT;Ingersoll SA;Ayyadurai S;Laroui H;Charania MA;Yan Y;Sitaraman SV;Merlin D
通讯作者：
Merlin D
影响因子：
3.1
作者：
Charania, Moiz A.;Laroui, Hamed;Merlin, Didier
通讯作者：
Merlin, Didier
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
12.4
作者：
Ehnfors, J.;Kost-Alimova, M.;Holmgren, L.
通讯作者：
Holmgren, L.