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Kindlin-2 Mediates Lipopolysaccharide-Induced Acute Lung Injury Partially via Pyroptosis in Mice

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Abstract

Acute lung injury (ALI) is characteristic of the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of pro-inflammatory leukocytes, and intractable hypoxemia, contributing to high mortality. Kindlin-2 is involved in the process of tumor- and wound healing-associated inflammation. However, the effects of kindlin-2 on lipopolysaccharide (LPS)-induced ALI and its mechanisms remain unknown. In this study, we found that the concentration of kindlin-2 was elevated in the lungs of ALI mice. The specific deletion of kindlin-2 by kindlin-2 siRNA attenuated the severity of lung injury, which was demonstrated by the reduced number of pro-inflammatory cells in bronchoalveolar lavage fluid and lung wet/dry weight ratio, and ameliorated pathologic changes in the lungs of ALI mice. Furthermore, kindlin-2 siRNA decreased the mRNA levels of pro-inflammatory factors (IL-1β, IL-6, and TNF-α) and the protein levels of pyroptosis-related proteins. In vitro studies confirmed that LPS + ATP promoted the expressions of pro-inflammatory factors and pyroptosis-related proteins, which was prevented by kindlin-2 siRNA pretreatment in endothelial cells (ECs). In conclusion, inhibition of kindlin-2 developes protective effects against LPS-induced ALI and the cytotoxicity of ECs, which may depend on blocking pyroptosis.

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The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

Funding

This work was supported by the High-level introduction of talent research start-up fund (LRYGCC202111, LRYGCC202108), Self-funded scientific research project of Health Commission of Guangxi (Z20210219, Z20200052), and Guangxi Natural Science Foundation (2020GXNSFAA297101).

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Author notes

  1. Yi-Dan Huang, Yu Fang contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Liuzhou Municipal People’s Hospital, Liuzhou, 545006, Guangxi, China

    Yi-Dan Huang, Li Ma, Wen-Long Li, Yi-Qi Zhou, Yuan-Hao Qin, Zhi-Jian You & Liang Dong

  2. Medical Laboratory and Pathology Center, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410021, Hunan, China

    Yu Fang

  3. Department of Anesthesiology, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545001, Guangxi, China

    Peng-Jiu Feng

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  1. Yi-Dan Huang
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Contributions

Liang Dong and Zhi-Jian You conceived and designed the experiments. Yi-Dan Huang, Yu Fang, Li Ma, and Yi-Qi Zhou performed the experiments. Wen-Long Li, Peng-Jiu Feng, and Yuan-Hao Qin analyzed the data. Liang Dong and Zhi-Jian You contributed reagents/materials/analysis tools. Yi-Dan Huang and Yu Fang wrote the paper. Liang Dong and Zhi-Jian You critically reviewed the manuscript. All authors had final approval of the submitted versions.

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Correspondence to Zhi-Jian You or Liang Dong.

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Animal Ethics Approval

All animal experiments were approved by Institutional Animals Care and Use Committee at Liuzhou Municipal People’s Hospital.

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Huang, YD., Fang, Y., Ma, L. et al. Kindlin-2 Mediates Lipopolysaccharide-Induced Acute Lung Injury Partially via Pyroptosis in Mice. Inflammation 45, 1199–1208 (2022). https://doi.org/10.1007/s10753-021-01613-w

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  • DOI: https://doi.org/10.1007/s10753-021-01613-w

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