Pathophysiological Significance of Neutrophilic Transfer RNA-Derived Small RNAs in Asymptomatic Moyamoya Disease.

Pathophysiological Significance of Neutrophilic Transfer RNA-Derived Small RNAs in Asymptomatic Moyamoya Disease.
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中性粒细胞转移 RNA 衍生的小 RNA 在无症状烟雾病中的病理生理学意义

DOI:
10.3390/cells10051086
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发表时间:
2021-05-01
期刊:
影响因子:
6
通讯作者:
Luo Y
Luo Y
中科院分区:
生物学2区
文献类型:
--
作者:
Li L;Liu P;Wang R;Huang Y;Luo J;Jiao L;Tao Z;Zheng Y;Fan J;Zhao H;Han Z;Luo Y

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了解目前治疗方案有限的无症状烟雾病(aMMD)是制定治疗策略的关键,这些策略将减缓该疾病的进展,并促进发现有症状烟雾病的治疗靶点。新发现的转移rna衍生的小rna (tsRNAs)在新生血管形成中发挥着潜在的调节作用,这是众所周知的烟雾病的病理表现。在这项研究中,使用下一代RNA测序技术对5名患者和5名匹配的健康受试者进行了aMMD中性粒细胞tsRNA转录组的分析。使用负二项广义对数线性回归来识别aMMD中的差异表达(DE)-tsRNAs。基因本体论和功能通路分析用于鉴定与DE-tsRNAs靶基因相关的生物学通路。选择4个tsRNAs,并使用定量逆转录聚合酶链反应进行验证。两组之间共有186个tsRNAs发生DE。病理生理事件,包括免疫反应、血管生成、轴突引导和代谢调节,富集了de - tsrna。四种de - tsrna的表达水平与嗜中性粒细胞转录组一致。这些异常表达的tsRNAs及其靶向病理生理过程为aMMD的潜在未来干预提供了基础。
Understanding asymptomatic moyamoya disease (aMMD), for which treatment options are currently limited, is key to the development of therapeutic strategies that will slow down the progression of this disease, as well as facilitate the discovery of therapeutic targets for symptomatic MMD. Newly found transfer RNA-derived small RNAs (tsRNAs) perform potential regulatory functions in neovascularization, which is a well-known pathological manifestation of MMD. In this study, the neutrophilic tsRNA transcriptome in aMMD was profiled using next-generation RNA sequencing in five patients and five matched healthy subjects. A negative binominal generalized log-linear regression was used to identify differentially expressed (DE)-tsRNAs in aMMD. Gene Ontology and functional pathway analyses were used to identify biological pathways involved with the targeted genes of the DE-tsRNAs. Four tsRNAs were selected and validated using quantitative reverse transcription polymerase chain reaction. In total, 186 tsRNAs were DE between the two groups. Pathophysiological events, including immune response, angiogenesis, axon guidance, and metabolism adjustment, were enriched for the DE-tsRNAs. The expression levels of the four DE-tsRNAs were consistent with those in the neutrophilic transcriptome. These aberrantly expressed tsRNAs and their targeted pathophysiological processes provide a basis for potential future interventions for aMMD.
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