The Second Clinical Medicine College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Pneumology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Bioengineered. 2022 Jan;13(1):697-708. doi: 10.1080/21655979.2021.2012621.
Regarding the extremely high mortality caused by sepsis-induced acute respiratory distress syndrome (ARDS), it is urgent to develop new biomarkers of sepsis-induced ARDS for treatment. Here, 532 differential expression genes (DEGs) related to sepsis and 433 DEGs related to sepsis-induced ARDS were screened in the GSE32707 dataset. Compared with sepsis samples, sepsis ARDS samples showed a higher infiltration of activated memory CD4 T cells and naive B cells, but a relatively lower infiltration of CD8 T cells. The pink and green modules which are significantly associated with sepsis-induced ARDS were then screened through co-expression network analysis. Differentially up-regulated GYPE and aberrantly down-regulated HSPB1, were subsequently found in the pink module of ARDS. CD81 and RPL22, two differentially low-expressed genes peculiar to ARDS, were identified in the green module. The function of CD81 was verified at the cellular level, and it was found that the up-regulation of CD81 in A549 could alleviate the LPS-induced injury of A549 cells. More importantly, the overexpressed CD81 can also increase the content of CD4 CD25 Foxp3 Treg in Jurkat cells, and after the co-culture of overexpressed CD81 Jurkat cells with LPS treatment A549 cells, the LPS-induced lung epithelial cell damage can be improved. Overall, four new plasma biomarker candidates were found in sepsis-induced ARDS, and we verified that CD81 may play critical roles in the biological and immunological processes of sepsis-induced ARDS.
针对脓毒症诱导的急性呼吸窘迫综合征（ARDS）导致的极高死亡率，急需开发新的脓毒症诱导的 ARDS 治疗生物标志物。本研究在 GSE32707 数据集筛选到 532 个与脓毒症相关的差异表达基因（DEGs）和 433 个与脓毒症诱导的 ARDS 相关的 DEGs。与脓毒症样本相比，脓毒症 ARDS 样本中激活的记忆 CD4 T 细胞和幼稚 B 细胞浸润较高，而 CD8 T 细胞浸润相对较低。通过共表达网络分析筛选出与脓毒症诱导的 ARDS 显著相关的粉红色和绿色模块。在 ARDS 的粉红色模块中，发现差异上调的 GYPE 和异常下调的 HSPB1。在绿色模块中鉴定出两个 ARDS 特有的差异低表达基因 CD81 和 RPL22。在细胞水平验证了 CD81 的功能，发现 A549 中 CD81 的上调可减轻 LPS 诱导的 A549 细胞损伤。更重要的是，过表达的 CD81 还可以增加 Jurkat 细胞中 CD4 CD25 Foxp3 Treg 的含量，并且在共培养过表达 CD81 Jurkat 细胞和 LPS 处理 A549 细胞后，可改善 LPS 诱导的肺上皮细胞损伤。总之，在脓毒症诱导的 ARDS 中发现了四个新的血浆生物标志物候选物，并且我们验证了 CD81 可能在脓毒症诱导的 ARDS 的生物学和免疫学过程中发挥关键作用。
