Effect and mechanism of apelin on lipopolysaccharide induced acute pulmonary vascular endothelial barrier dysfunction

• Published in: Scientific reports 2023-01, Vol.13 (1), p.1560-1560, Article 1560
• Main Authors: Huang, Tianpeng, Chen, Danyang, Ye, Wei, Chen, Wenwen, Zhang, Min, Hao, Jiale, Xu, Licong, Bai, Xiaoqing, Mao, Sunzhong
• Format: Article
• Language: English
• Subjects: 631/154; 631/80; 692/420/254; 692/699; 692/699/1785; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Animals; Apelin - metabolism; Blood vessels; Bronchus; Cadherins; Correlation analysis; FLI-1 protein; Gene expression; Humanities and Social Sciences; Immunofluorescence; Inflammation; Irinotecan; Lavage; Leukemia; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lung - metabolism; Lungs; Mice; Mortality; multidisciplinary; Permeability; Proteins; Science; Science (multidisciplinary); Src protein; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptors; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-27889-6

Vascular endothelial barrier dysfunction is the most prominent manifestation and important cause of mortality in infectious acute lung injury (ALI). Exogenous apelin is effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory response in ALI lungs, reducing exudation of lung tissue and decreasing mortality. This study set out to investigate the association between apelin and Friend leukemia integration-1 (Fli-1) in the prevention and treatment of ALI, and to elucidate the molecular mechanism by which apelin protects the permeability of the vascular endothelial barrier. At the vivo functional level, lung wet/dry weight ratio was used to detect whole lung permeability, evans blue assay and dual fluorescent protein tracking assay were used to detect lung vascular endothelial permeability, HE staining to observe the inflammatory status of lung tissue, and immunofluorescence staining for VE-cadherin expression levels in blood vessels. The changes in inflammatory factors in bronchoalveolar lavage fluid (BALF) were detected by ELASA. Western blot was used to detect the expression level of proteins. qRT-PCR was performed to detect changes in mRNA expression of Fli-1 and adherent junction-related proteins. The correlation analysis of Fli-1 with vascular endothelial permeability and SRC showed that Fli-1 participated in the process of ALI. After preventive and therapeutic treatment of ALI mice with exogenous apelin, Fli-1, APJ, VE-cadherin, phosphorylated-VE-cadherin (p-VE-cadherin) and β-catenin were up-regulated, while SRC, phosphorylated-SRC (p-SRC), VEGF and VEGF-R were down-regulated, which indicated that the stability of vascular endothelial barrier was enhanced. With the use of Fli-1 inhibitor irinotecan, the protective effect of apelin was weakened in various functional indexes, genes and proteins. The lung was maintained at the level of the injury. Our research shows that Fli-1 is involved in the LPS-induced ALI process. The molecular mechanism for apelin in preventing endothelial barrier dysfunction in ALI is through up-regulating Fli-1, thus regulating adherens junction-related proteins, and finally recovering the endothelial barrier function.