Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host Disease in the Rat.
Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host Disease in the Rat.
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DOI：
10.3389/fimmu.2016.00361
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发表时间：
2016
影响因子：
7.3
通讯作者：
Inngjerdingen M
中科院分区：
文献类型：
--
作者：
Jalapothu D;Boieri M;Crossland RE;Shah P;Butt IA;Norden J;Dressel R;Dickinson AM;Inngjerdingen M
MicroRNA (miRNA) 已成为多种生物过程的中央调节因子，并有助于驱动多种疾病的病理。急性移植物抗宿主病 (aGvHD) 是同种异体造血干细胞移植后的主要并发症，由同种异体反应性供体 T 细胞攻击宿主组织导致炎症和组织破坏引起。 aGvHD 期间 miRNA 表达模式发生变化，我们假设我们可以识别 aGvHD 靶组织中的 miRNA 特征，这可能有助于了解该疾病的潜在分子病理学。我们利用 aGvHD 大鼠模型，移植完全 MHC 不匹配的 T 细胞耗尽的骨髓，然后输注供体 T 细胞。利用 NanoString 杂交平台，结合定量 PCR 验证，研究了 423 种大鼠 miRNA 在皮肤、肠道、肺组织和肠道 T 细胞中的表达模式。 MHC 匹配的移植大鼠作为对照。在皮肤中，观察到 miR-34b 上调和 miR-326 下调，而在肠道中，我们检测到 miR-743b 下调和 miR-345-5p 下调趋势。因此，观察到了 miRNA 的组织特异性表达模式。 miR-326 和 miR-743b 此前均未与 aGvHD 相关。此外，我们发现患有 aGvHD 的大鼠皮肤组织中 miR-146a 和 miR-155 上调。肠道 T 细胞分析表明，aGvHD 和对照之间有 23 种 miRNA 受到差异性调节。其中两个 miRNA 在皮肤 (miR-326) 或肠道 (miR-345-5p) 组织中差异表达。肠道和外周血 T 细胞的比较表明 miR-99a、miR-223、miR-326 和 miR-345-5p 普遍存在表达失调。对这些 miRNA 的预测基因靶标的分析表明，它们可能靶向皮肤和肠道中的炎症网络，从而进一步调节炎症细胞因子的产生。总之，对患有 aGvHD 的大鼠进行全面的 miRNA 分析表明，miRNA 表达模式存在组织特异性差异，而仅通过外周血 T 细胞分析可能无法检测到这种差异。这些组织特异性 miRNA 可能有助于不同的病理机制，并可能代表潜在的治疗靶点。
MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate inflammatory cytokine production. In conclusion, comprehensive miRNA profiling in rats suffering from aGvHD demonstrate tissue-specific differences in the expression patterns of miRNA that may not be detected by profiling of peripheral blood T cells alone. These tissue-specific miRNAs may contribute to distinct pathologic mechanisms and could represent potential targets for therapy.
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影响因子：
30.5
作者：
Du, Changsheng;Liu, Chang;Pei, Gang
通讯作者：
Pei, Gang
影响因子：
7.3
作者：
Atarod, Sadaf;Ahmed, Mohammed Mahid;Dickinson, Anne Mary
通讯作者：
Dickinson, Anne Mary
影响因子：
56.9
作者：
Thai, To-Ha;Calado, Dinis Pedro;Rajewsky, Klaus
通讯作者：
Rajewsky, Klaus
影响因子：
32.4
作者：
Hanash AM;Dudakov JA;Hua G;O'Connor MH;Young LF;Singer NV;West ML;Jenq RR;Holland AM;Kappel LW;Ghosh A;Tsai JJ;Rao UK;Yim NL;Smith OM;Velardi E;Hawryluk EB;Murphy GF;Liu C;Fouser LA;Kolesnick R;Blazar BR;van den Brink MR
通讯作者：
van den Brink MR
DOI：
10.1523/jneurosci.4966-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kefas B;Comeau L;Floyd DH;Seleverstov O;Godlewski J;Schmittgen T;Jiang J;diPierro CG;Li Y;Chiocca EA;Lee J;Fine H;Abounader R;Lawler S;Purow B
通讯作者：
Purow B