Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Department of Critical Care Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Sci Rep. 2024 Sep 2;14(1):20400. doi: 10.1038/s41598-024-71771-y.
To select the core target (RAB13) in sepsis patients' peripheral blood and investigate its molecular functions and possible mechanisms. The peripheral blood of sepsis patients (n = 21) and healthy individuals (n = 9) within 24 h after admission were collected for RNA-seq, and differential gene screening was performed by iDEP online analysis software (P < 0.01; log2FC ≥ 2) and enrichment analysis, the potential core target RAB13 was screened out. The association between RAB13 expression and sepsis severity was explored using multiple datasets in the GEO database, and survival analysis was conducted. Subsequently, peripheral blood mononuclear cells (PBMCs) from sepsis and control groups were isolated, and 10 × single-cell sequencing was used to identify the main RAB13-expressing cell types. Finally, LPS was used to stimulate THP1 cells to construct a sepsis model to explore the function and possible mechanism of RAB13. We found that RAB13 was a potential core target, and RAB13 expression level was positively associated with sepsis severity and negatively correlated with survival based on multiple public datasets. A single-cell sequencing indicated that RAB13 is predominantly localized in monocytes. Cell experiments validated that RAB13 is highly expressed in sepsis, and the knockdown of RAB13 promotes the polarization of macrophages towards the M2 phenotype. This mechanism may be associated with the ECM-receptor interaction signaling pathway. The upregulation of RAB13 in sepsis patients promotes the polarization of M2-like macrophages and correlates positively with the severity of sepsis.
为了在脓毒症患者外周血中选择核心靶标（RAB13），并研究其分子功能和可能的机制。在入院后 24 小时内收集脓毒症患者（n=21）和健康个体（n=9）的外周血，进行 RNA-seq，通过 iDEP 在线分析软件进行差异基因筛选（P<0.01；log2FC≥2）和富集分析，筛选出潜在的核心靶标 RAB13。使用 GEO 数据库中的多个数据集探索 RAB13 表达与脓毒症严重程度的相关性，并进行生存分析。随后，分离脓毒症组和对照组的外周血单核细胞（PBMCs），并进行 10×单细胞测序，以鉴定主要表达 RAB13 的细胞类型。最后，使用 LPS 刺激 THP1 细胞构建脓毒症模型，以探索 RAB13 的功能和可能的机制。我们发现 RAB13 是一个潜在的核心靶标，基于多个公共数据集，RAB13 表达水平与脓毒症严重程度呈正相关，与生存呈负相关。单细胞测序表明 RAB13 主要定位于单核细胞。细胞实验验证了 RAB13 在脓毒症中高表达，并且 RAB13 的敲低促进巨噬细胞向 M2 表型极化。这种机制可能与 ECM-受体相互作用信号通路有关。脓毒症患者中 RAB13 的上调促进 M2 样巨噬细胞的极化，并与脓毒症的严重程度呈正相关。
