Shi Mingjie, Wei Yue, Guo Runmin, Luo Fei
Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, People's Republic of China.
Matenal and Child Research Institute, Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, People's Republic of China.
J Inflamm Res. 2024 Apr 15;17:2285-2298. doi: 10.2147/JIR.S456132. eCollection 2024.
Sepsis is a major contributor to morbidity and mortality among hospitalized patients. This study aims to identify markers associated with the severity and prognosis of sepsis, providing new approaches for its management and treatment.
Data were mined from the Gene Expression Omnibus (GEO) databases and were analyzed by multiple statistical methods like the Spearman correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, and functional enrichment analysis. Candidate indicator' associations with immune infiltration and roles in sepsis development were evaluated. Additionally, we employed techniques such as flow cytometry and neutral red staining to evaluate its impact on macrophage functions like polarization and phagocytosis.
Twenty-eight genes were identified as being closely linked to the severity of sepsis, among which transforming growth factor beta induced (TGFBI) emerged as a distinct marker for predicting clinical outcomes. Notably, reductions in TGFBI expression during sepsis correlate with poor prognosis and rapid disease progression. Elevated expression of TGFBI has been observed to mitigate abnormalities in sepsis-related immune cell infiltration that are critical to the pathogenesis and prognosis of the disease, including but not limited to type 17 T helper cells and activated CD8 T cells. Moreover, the protein-protein interaction network revealed the top ten genes that interact with TGFBI, showing significant involvement in the regulation of the actin cytoskeleton, extracellular matrix-receptor interactions, and phagosomes. These are pivotal elements in the formation of phagocytic cups by macrophages, squaring the findings of the Human Protein Atlas. Additionally, we discovered that TGFBI expression was significantly higher in M2-like macrophages, and its upregulation was found to inhibit lipopolysaccharide-induced polarization and phagocytosis in M1-like macrophages, thereby playing a role in preventing the onset of inflammation.
TGFBI warrants additional exploration as a promising biomarker for assessing illness severity and prognosis in patients with sepsis, considering its significant association with immunological and inflammatory responses in this condition.
脓毒症是住院患者发病和死亡的主要原因。本研究旨在确定与脓毒症严重程度和预后相关的标志物，为其管理和治疗提供新方法。
从基因表达综合数据库（GEO）中挖掘数据，并通过多种统计方法进行分析，如Spearman相关系数、Kaplan-Meier分析、Cox回归分析和功能富集分析。评估候选指标与免疫浸润的关联及其在脓毒症发展中的作用。此外，我们采用流式细胞术和中性红染色等技术来评估其对巨噬细胞极化和吞噬等功能的影响。
确定了28个与脓毒症严重程度密切相关的基因，其中转化生长因子β诱导基因（TGFBI）成为预测临床结局的独特标志物。值得注意的是，脓毒症期间TGFBI表达降低与预后不良和疾病快速进展相关。已观察到TGFBI表达升高可减轻脓毒症相关免疫细胞浸润异常，这些异常对疾病的发病机制和预后至关重要，包括但不限于17型辅助性T细胞和活化的CD8 T细胞。此外，蛋白质-蛋白质相互作用网络揭示了与TGFBI相互作用的前十个基因，显示它们在肌动蛋白细胞骨架调节、细胞外基质-受体相互作用和吞噬体中具有重要作用。这些是巨噬细胞形成吞噬杯的关键要素，与人类蛋白质图谱的研究结果相符。此外，我们发现TGFBI在M2样巨噬细胞中的表达明显更高，并且发现其上调可抑制脂多糖诱导的M1样巨噬细胞极化和吞噬作用，从而在预防炎症发作中发挥作用。
鉴于TGFBI与脓毒症患者的免疫和炎症反应密切相关，它作为评估脓毒症患者疾病严重程度和预后的有前景的生物标志物值得进一步探索。
