Wen Jake J, Mobli Keyan, Radhakrishnan Geetha L, Radhakrishnan Ravi S
Department of Surgery University of Texas Medical Branch, Galveston, TX 77550, USA.
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77550, USA.
J Pers Med. 2022 Jun 20;12(6):1007. doi: 10.3390/jpm12061007.
Immune cascade is one of major factors leading to cardiac dysfunction after burn injury. TLRs are a class of pattern-recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen. The Rat Toll-Like Receptor (TLR) Signaling Pathway RT² Profiler PCR Array profiles the expression of 84 genes central to TLR-mediated signal transduction and innate immunity, and is a validated tool for identifying differentially expressed genes (DEGs). We employed the PCR array to identify burn-induced cardiac TLR-signaling-related DEGs. A total of 38 up-regulated DEGs and 19 down-regulated DEGs were identified. Network analysis determined that all DEGS had 10 clusters, while up-regulated DEGs had 6 clusters and down-regulated DEGs had 5 clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were involved in TLR signaling, the RIG-I-Like receptor signaling pathway, the IL-17 signaling pathway, and the NFkB signaling pathway. Function analysis indicated that DEGs were associated with Toll-like receptor 2 binding, Lipopeptide binding, Toll-like receptor binding, and NAD(P)+ nucleosidase activity. The validation of 18 up-regulated DEGs (≥10-fold change) and 6 down-regulated DEGs (≤5-fold change) demonstrated that the PCR array is a trusted method for identifying DEGs. The analysis of validated DEG-derived protein-protein interaction networks will guide our future investigations. In summary, this study not only identified the TLR-signaling-pathway-related DEGs after burn injury, but also confirmed that the burn-induced cardiac cytokine cascade plays an important role in burn-induced heart dysfunction. The results will provide the novel therapeutic targets to protect the heart after burn injury.
免疫级联反应是烧伤后导致心脏功能障碍的主要因素之一。Toll样受体（TLRs）是一类模式识别受体（PRRs），通过感知保守的分子模式启动先天免疫反应，以便对病原体进行早期免疫识别。大鼠Toll样受体（TLR）信号通路RT² Profiler PCR阵列可分析84个对TLR介导的信号转导和先天免疫至关重要的基因的表达情况，是鉴定差异表达基因（DEGs）的有效工具。我们使用该PCR阵列来鉴定烧伤诱导的与心脏TLR信号相关的DEGs。共鉴定出38个上调的DEGs和19个下调的DEGs。网络分析确定所有DEGs有10个聚类，而上调的DEGs有6个聚类，下调的DEGs有5个聚类。京都基因与基因组百科全书（KEGG）分析表明，DEGs参与TLR信号通路、视黄酸诱导基因I样受体信号通路、白细胞介素-17信号通路和核因子κB信号通路。功能分析表明，DEGs与Toll样受体2结合、脂肽结合、Toll样受体结合以及NAD(P)+核苷酶活性相关。对18个上调的DEGs（≥10倍变化）和6个下调的DEGs（≤5倍变化）的验证表明，该PCR阵列是鉴定DEGs的可靠方法。对经验证的DEG衍生的蛋白质-蛋白质相互作用网络的分析将指导我们未来的研究。总之，本研究不仅鉴定了烧伤后与TLR信号通路相关的DEGs，还证实了烧伤诱导的心脏细胞因子级联反应在烧伤诱导的心脏功能障碍中起重要作用。这些结果将为烧伤后心脏保护提供新的治疗靶点。
