Shen Ye, Ye Xiangming, Jiang Lingzhi, Li Hengjie, Zhang Yanli, Wang Wenmin, Mao Hui
Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Curr Mol Med. 2025 Apr 17. doi: 10.2174/0115665240338945250317082242.
The calcium-binding protein S100A12 plays a pivotal role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the underlying mechanisms are yet to be fully elucidated.
This study aimed to investigate the role of S100A12 in LPS-induced injury of human pulmonary microvascular endothelial cells (HPMECs) and its molecular regulatory mechanism.
An in vitro model of ALI/ARDS was established by lipopolysaccharide (LPS)-induced HPMECs. CCK-8, flow cytometry assay, and ELISA were used to detect the cell viability, apoptosis, and inflammation. The integrity of the endothelial barrier was assessed by tube formation assay and VE-cadherin and occludin protein levels. The molecular mechanism of S100A12 was analyzed by transcriptomics and validated using qRT-PCR and western blotting analyses.
S100A12 expression was significantly elevated in LPS-stimulated HPMECs, and S100A12 knockdown alleviated LPS-induced apoptosis, inflammation, and endothelial barrier dysfunction in HPMECs. Transcriptomic analysis revealed the potential gene network mapping regulated by LPS stimulation and S100A12 knockdown. Differentially expressed genes were significantly enriched in the JAK2/STAT3 signaling pathway as verified by western blotting analysis.
Our results suggested S100A12 to be significantly upregulated in LPSinduced HPMECs; inhibiting S100A12 can alleviate endothelial cell barrier dysfunction through the JAK2/STAT3 signaling pathway and thereby improve LPS-induced HPMECs injury.
钙结合蛋白S100A12在急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）的进展中起关键作用。然而，其潜在机制尚未完全阐明。
本研究旨在探讨S100A12在脂多糖（LPS）诱导的人肺微血管内皮细胞（HPMECs）损伤中的作用及其分子调控机制。
通过脂多糖（LPS）诱导HPMECs建立ALI/ARDS体外模型。采用CCK-8、流式细胞术和ELISA检测细胞活力、凋亡和炎症。通过管形成试验以及VE-钙黏蛋白和闭合蛋白水平评估内皮屏障的完整性。通过转录组学分析S100A12的分子机制，并使用qRT-PCR和蛋白质印迹分析进行验证。
S100A12在LPS刺激的HPMECs中表达显著升高，敲低S100A12可减轻LPS诱导的HPMECs凋亡、炎症和内皮屏障功能障碍。转录组分析揭示了LPS刺激和S100A12敲低所调控的潜在基因网络图谱。蛋白质印迹分析证实差异表达基因在JAK2/STAT3信号通路中显著富集。
我们的结果表明，S100A12在LPS诱导的HPMECs中显著上调；抑制S100A12可通过JAK2/STAT3信号通路减轻内皮细胞屏障功能障碍，从而改善LPS诱导的HPMECs损伤。
