Department of Neonatology, The Affiliated Hospital of Putian University, Putian, 351100, China.
J Cardiothorac Surg. 2023 Mar 24;18(1):92. doi: 10.1186/s13019-023-02186-5.
Streptococcus pneumoniae (Spn) is a common pathogen for pediatric pneumonia and leads to severe lung injury. This study is conducted to analyze the role of F-box and leucine rich repeat protein 19 (FBXL19) in Spn-induced lung injury in immature mice.
Immature mice were infected with Spn to record the survival rates and bacterial loads in bronchoalveolar lavage fluid. Levels of FBXL19 and FOXM1 in lung tissues were determined via real-time quantitative polymerase chain reaction or Western blotting. After the interference of FBXL19, its impacts on lung inflammatory injury were appraised by the lung wet/dry weight ratio, myeloperoxidase activity, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The binding of FBXL19 to forkhead box M1 (FOXM1) in mouse lung epithelial cells was determined. After MG132 treatment, the protein and ubiquitination levels of FOXM1 were measured. The functional rescue experiments were performed to analyze the role of FOXM1 in FBXL19-regulated lung injury.
FBXL19 was downregulated while FOXM1 was upregulated in lung tissues of Spn-infected immature mice. Overexpression of FBXL19 reduced the degree of lung injury and inflammation. FBXL19 can bind to FOXM1 to reduce its protein level via ubiquitination degradation. MG132 reduced the ubiquitination and increased the protein level of FOXM1. Overexpression of FOXM1 reversed the protective role of FBXL19 overexpression in lung injury of Spn immature mice.
FBXL19 was downregulated by Spn and FBXL19 overexpression alleviated lung injury by inducing ubiquitination and degradation of FOXM1 in Spn immature mice.
肺炎链球菌（Spn）是小儿肺炎的常见病原体，可导致严重的肺损伤。本研究旨在分析 F -box 和富含亮氨酸重复蛋白 19（FBXL19）在 Spn 诱导的未成熟小鼠肺损伤中的作用。
用 Spn 感染未成熟小鼠，记录存活率和支气管肺泡灌洗液中的细菌载量。通过实时定量聚合酶链反应或 Western blot 测定肺组织中 FBXL19 和 FOXM1 的水平。干扰 FBXL19 后，通过肺湿/干重比、髓过氧化物酶活性、苏木精和伊红染色以及酶联免疫吸附试验评估其对肺炎症损伤的影响。测定 FBXL19 在小鼠肺上皮细胞中与叉头框 M1（FOXM1）的结合。MG132 处理后，测定 FOXM1 的蛋白和泛素化水平。进行功能挽救实验，分析 FOXM1 在 FBXL19 调节的肺损伤中的作用。
Spn 感染未成熟小鼠肺组织中 FBXL19 下调，FOXM1 上调。FBXL19 的过表达减轻了肺损伤和炎症的程度。FBXL19 可以通过泛素化降解与 FOXM1 结合，降低其蛋白水平。MG132 减少泛素化并增加 FOXM1 的蛋白水平。FOXM1 的过表达逆转了 FBXL19 过表达对 Spn 未成熟小鼠肺损伤的保护作用。
Spn 下调 FBXL19，FBXL19 过表达通过诱导 Spn 未成熟小鼠中 FOXM1 的泛素化和降解减轻肺损伤。
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