Ye Shen, Xiangming Ye, Lingzhi Jiang, Hengjie Li, Yanli Zhang, Wenmin Wang, Hui Mao
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引用次数: 0
Abstract
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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