Zhu Zhipeng, Ling Xiaoyan, Zhou Hongmei, Xie Junran
Department of Anaesthesiology, The Second Affiliated Hospital of Jiaxing University, Zhejiang, 314000, China.
Department of Outpatient Nursing, The Second Affiliated Hospital of Jiaxing University, Zhejiang, 314000, China.
Heliyon. 2023 Jul 23;9(8):e18600. doi: 10.1016/j.heliyon.2023.e18600. eCollection 2023 Aug.
Vascular endothelial cell dysfunction involving syndecan (SDC) proteoglycans contributes to acute sepsis-associated lung injury (ALI), but the exact SDC isoform involved is unclear. We aimed to clarify which SDCs are involved in ALI. A relevant gene expression dataset (GSE5883) was analysed for differentially expressed genes (DEGs) between lipopolysaccharide (LPS)-treated and control lung endothelial cells and for SDC isoform expression. Bioinformatic analyses to predict DEG function were conducted using R language, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes. SDC2 and SDC4 expression profiles were examined under inflammatory conditions in human lung vascular endothelial cell and mouse sepsis-associated ALI models. Transcription factors regulating SDC2/4 were predicted to indirectly assess SDC involvement in septic inflammation. Of the DEGs, 224 and 102 genes were up- and downregulated, respectively. Functional analysis indicated that DEGs were involved in modulating receptor ligand and signalling receptor activator activities, cytokine receptor binding, responses to LPS and molecules of bacterial origin, regulation of cell adhesion, tumour necrosis factor signalling, and other functions. DEGs were also enriched for cytoplasmic ribonucleoprotein granules, transcription regulator complexes, and membrane raft cellular components. gene expression was 4.5-fold higher in the LPS group than in the control group, while levels were similar in both groups. SDC4 mRNA and protein expression was markedly upregulated in response to inflammatory injury, and SDC4 downregulation severely exacerbated inflammatory responses in both and models. Overall, our data demonstrate that SDC4, rather than SDC2, is involved in LPS-induced sepsis-associated ALI.
涉及Syndecan（SDC）蛋白聚糖的血管内皮细胞功能障碍会导致急性脓毒症相关肺损伤（ALI），但具体涉及的SDC亚型尚不清楚。我们旨在阐明哪些SDC参与了ALI。分析了一个相关基因表达数据集（GSE5883），以确定脂多糖（LPS）处理的肺内皮细胞与对照肺内皮细胞之间的差异表达基因（DEG）以及SDC亚型的表达情况。使用R语言、基因本体论和京都基因与基因组百科全书对预测DEG功能的生物信息学分析。在人肺血管内皮细胞和小鼠脓毒症相关ALI模型的炎症条件下，检测了SDC2和SDC4的表达谱。预测调节SDC2/4的转录因子，以间接评估SDC在脓毒症炎症中的参与情况。在这些DEG中，分别有224个和102个基因上调和下调。功能分析表明，DEG参与调节受体配体和信号受体激活剂活性、细胞因子受体结合、对LPS和细菌来源分子的反应、细胞粘附调节、肿瘤坏死因子信号传导及其他功能。DEG还在细胞质核糖核蛋白颗粒、转录调节复合物和膜筏细胞成分中富集。LPS组的基因表达比对照组高4.5倍，而两组的水平相似。在炎症损伤反应中，SDC4的mRNA和蛋白表达明显上调，在人和小鼠模型中，SDC4的下调都严重加剧了炎症反应。总体而言，我们的数据表明，参与LPS诱导的脓毒症相关ALI的是SDC4，而非SDC2。
