Abstract
Hemorrhage shock (HS) is a major threat to patients with trauma and spontaneous bleeding, resulting in multi-organ failure including the kidney. Tyrosine kinase nonreceptor 1 (TNK1) has been shown to be upregulated in the kidney of experimental HS and patients with severe trauma. The study aims to investigate the role of TNK1 and the underlying mechanism in HS-induced kidney injury. A model of HS was established with femoral artery bloodletting, followed by resuscitation in Sprague–Dawley rats. Renal expression of TNK1 was abnormally induced by HS in rats. Knockdown of TNK1 alleviated HS-induced cell apoptosis and the level of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) in the kidney. The expression of M1 macrophage markers (CD86 and iNOS) and the activation of STAT1 were inhibited by TNK1 knockdown in HS rats. In vitro, human monocyte THP-1 cells were treated with 20 ng/mL interferon-gamma plus 100 ng/mL lipopolysaccharide to induce M1 polarization. TNK1 knockdown exerted inhibitory effect on macrophage M1 polarization, M1-type inflammatory cytokine production and STAT1 activation in THP-1 cells. In conclusion, downregulation of TNK1 alleviates HS-induced kidney injury by suppressing macrophage M1 polarization, inflammation and kidney cell apoptosis, in which the deactivation of STAT1 signaling may be involved.
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Acknowledgements
The current study was supported by the Precision Medicine Projects of Wuxi Municipal Healthy Commission (Grant no. J202007).
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All persons who meet authorship criteria are listed as authors. XG and SS contributed to the conception of the work. MLT and JMC performed the experiments. YW and ZRH analyzed the data. HY drafted the manuscript. CX revised the manuscript.
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The animal experiments were approved by the Ethics Committee of Wuxi 9th Affiliated Hospital of Soochow University (No. KT2020029).
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Tang, M., Cai, J., Wang, Y. et al. Tyrosine kinase nonreceptor 1 (TNK1) knockdown ameliorates hemorrhage shock-induced kidney injury via inhibiting macrophage M1 polarization. 3 Biotech 11, 501 (2021). https://doi.org/10.1007/s13205-021-03042-w
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DOI: https://doi.org/10.1007/s13205-021-03042-w