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线粒体移植对多微生物脓毒症模型转录组学的影响。

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

机构信息

School of Biological Science and Technology, Chonnam National University, Gwangju 61186, Republic of Korea.

Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Oct 18;24(20):15326. doi: 10.3390/ijms242015326.

DOI:10.3390/ijms242015326
PMID:37895006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10607172/
Abstract

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, = 10), sepsis-induced (SEPSIS, = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. and were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (, , , 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

摘要

先前，我们证实了线粒体移植在多微生物脓毒症模型中具有有益效果。然而，其机制尚未被充分研究。线粒体拥有其自身的基因，脓毒症中的基因组变化是病理生理学、生物标志物和治疗靶点的一个重要问题。为了研究多微生物脓毒症模型中线粒体移植后转录组特征的变化，我们使用了大鼠粪便多微生物脓毒症模型。从假手术（SHAM，n = 10）、脓毒症诱导（SEPSIS，n = 7）和接受线粒体移植的脓毒症（SEPSIS + MT，n = 8）大鼠的脾细胞中提取总 RNA，然后在三组之间进行比较转录组全谱分析。我们还使用 qPCR 对这些结果进行了验证。在被映射为线粒体的读段百分比方面，SEPSIS + MT 组的映射比例明显高于其他两组。与 SEPSIS 相比，在 SEPSIS + MT 中 和 被鉴定为高表达。将 SHAM 的表达水平作为另一个对照变量，我们进一步鉴定了六个基因（、、、7SK、SNORD94 和 SNORA53），这些基因在脓毒症诱导后表达上调，并且观察到它们的表达水平在经过线粒体移植后被减弱。在脓毒症中进行线粒体移植后鉴定出了转录组特征的变化。这可能为探索线粒体移植在脓毒症中的机制提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e9/10607172/4d42491da01c/ijms-24-15326-g006.jpg
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Delivery of mitochondria confers cardioprotection through mitochondria replenishment and metabolic compliance.
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