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Bovine lactoferrin inhibits inflammatory response and apoptosis in lipopolysaccharide-induced acute lung injury by targeting the PPAR-γ pathway

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Abstract

Background

Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein. Previous studies have demonstrated that LF may be a potential drug for treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in ALI using the RNA sequencing (RNA-seq) technology and transcriptome analysis.

Methods and results

Based on the differentially expressed genes (DEGs) obtained from RNA-seq of the Lung from mouse model, the bioinformatics workflow was implemented using the BGISEQ-500 platform. The protein–protein interaction (PPI) network was obtained using STRING, and the hub gene was screened using Cytoscape. To verify the results of transcriptome analysis, the effects of bLF on Lipopolysaccharide (LPS)-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via Cell Counting Kit-8 (CCK-8) test, active oxygen detection test, ELISA, and western blot assay.

Transcriptome analysis revealed that two hub gene modules of DEGs were screened via PPI analysis using the STRING and MCODE plug-ins of Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these core modules are enriched in the PPAR (peroxisome proliferator-activated receptor) and AMPK (AMP-activated protein kinase) signaling pathways. Through cell experiments, our study shows that bLF can inhibit ROS, inflammatory reaction, and LPS-induced BEAS-2B cell apoptosis, which are significantly antagonized by the PPAR-γ inhibitor GW9662.

Conclusion

This study has suggested that the PPAR-γ pathway is the critical target of bLF in anti-inflammatory reactions and apoptosis of ALI, which provides a direction for further research.

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Data availability

The mRNA Sequence data that support the findings of this study have been deposited in the Gene Expression Omnibus with the GSE numbe GSE247266.

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Funding

This study was financially supported by the Mandatory subject of Hebei Provincial Administration of Traditional Chinese Medicine [No.: 2021027].

Author information

Author notes

  1. Yantao Li, Junhu Li and Yan Dong have contributed equally to this work.

Authors and Affiliations

  1. Department of Critical Care Medicine, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050000, China

    Yantao Li & Can Wang

  2. Emergency Department, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050000, China

    Junhu Li & Yan Dong

  3. The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China

    Zhigang Cai

  4. Hebei Key Laboratory of Respiratory Critical Care Medicine, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China

    Zhigang Cai

  5. Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China

    Zhigang Cai

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  1. Yantao Li
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  2. Junhu Li
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  3. Yan Dong
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  4. Can Wang
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Contributions

YL and ZC contributed to the study design and material preparation. JL and YD performed the experiments. WC performed the statistical analysis. YL drafted the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Zhigang Cai.

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The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

All mouse experiments were approved by the Experimental Ethics Committee of Hebei University of Chinese Medicine (Numbering: DWLL2019023).

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Li, Y., Li, J., Dong, Y. et al. Bovine lactoferrin inhibits inflammatory response and apoptosis in lipopolysaccharide-induced acute lung injury by targeting the PPAR-γ pathway. Mol Biol Rep 51, 492 (2024). https://doi.org/10.1007/s11033-024-09436-2

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