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与人类坏死性小肠结肠炎相关的白细胞介素-17相关特征基因。

IL-17-related signature genes linked to human necrotizing enterocolitis.

作者信息

Tremblay Éric, Ferretti Emanuela, Babakissa Corentin, Burghardt Karolina Maria, Levy Emile, Beaulieu Jean-François

机构信息

Laboratory of Intestinal Physiopathology, Faculté de médecine et sciences de la santé, Université de Sherbrooke, Main Building Room 9425, Sherbrooke, QC, J1H 5N4, Canada.

Division of Neonatology, Department of Pediatrics, CHEO, Ottawa, ON, Canada.

出版信息

BMC Res Notes. 2021 Mar 4;14(1):82. doi: 10.1186/s13104-021-05489-9.

Abstract

OBJECTIVE

Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units all over the world. The objective of the present study was to take advantage of RNA-Seq data from the analysis of intestinal specimens of preterm infants diagnosed with NEC. Function enrichments with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyse previous data in order to identify biological and functional processes, which could provide more insight into the pathogenesis of NEC in infants.

RESULTS

Gene set enrichment analysis indicated that the most significant biological pathways over-represented in NEC neonates were closely associated with innate immune functions. One of the striking observations was the highly modulated expression of inflammatory genes related to the IL-17 pathway including such as pro-inflammatory cytokines (CXCL8), chemokines (CXCL5 and CXCL10) and antimicrobials (DEF5A, DEF6A, LCN2, NOS2) in the intestine of neonates diagnosed with NEC. Interestingly, the increase in IL-17 expression appeared to be under the IL-17F form, as reported in Crohn's disease, another inflammatory bowel disease. Further investigation is thus still needed to determine the precise role of IL-17F and its downstream targets in NEC.

摘要

目的

坏死性小肠结肠炎(NEC)是全球新生儿重症监护病房中早产儿最常见的危及生命的胃肠道疾病。本研究的目的是利用对诊断为NEC的早产儿肠道标本分析所得的RNA测序数据。运用基因本体论和京都基因与基因组百科全书进行功能富集分析,以分析先前的数据,从而确定生物学和功能过程,这可为深入了解婴儿NEC的发病机制提供更多信息。

结果

基因集富集分析表明,NEC新生儿中过度代表的最显著生物学途径与先天免疫功能密切相关。一个显著的观察结果是,在诊断为NEC的新生儿肠道中,与IL-17途径相关的炎症基因表达受到高度调节,包括促炎细胞因子(CXCL8)、趋化因子(CXCL5和CXCL10)和抗菌物质(DEF5A、DEF6A、LCN2、NOS2)。有趣的是,正如在另一种炎症性肠病克罗恩病中所报道的那样,IL-17表达的增加似乎是以IL-17F形式出现的。因此,仍需要进一步研究以确定IL-17F及其下游靶点在NEC中的精确作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae50/7934396/955bc54903e8/13104_2021_5489_Fig1_HTML.jpg

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