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LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1 alpha

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Abstract

Background

Sepsis is a commonly seen severe case in clinical practice and the main cause of health loss worldwide.

Objective

We investigated the biological function of LRG1 and its underlying molecular mechanisms in sepsis-renal injury. Mice of sepsis model group were subjected to cecal ligation and puncture (CLP) surgery after anesthetization. THP-1 cell was induced by LPS for vitro model.

Results

The mRNA and protein levels of LRG1 in renal tissue of sepsis model were reduced. LRG1 could reduce the inflammation reaction in model of sepsis-renal injury. In addition, LRG1 up-regulation reduced inflammation reaction and ROS production levels in vitro model via the activation of HIF-1α and suppression of NLRP3 inflammasome. Knockout of LRG1 increased inflammation reaction and ROS production levels in vitro model via the inactivation of HIF-1α and induction of NLRP3 inflammasome. Furthermore, the inhibition of HIF-1α reduced the effects of LRG1 on NLRP3 inflammasome in vitro model.

Conclusions

The present study suggests that LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1α, thereby may be a promising therapeutic target of sepsis-renal injury.

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Author notes

  1. Wenjing Du and Yiquan Sang are co-first authors of this study.

Authors and Affiliations

  1. Department of Critical Care Medicine, Xuzhou Central Hospital, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, 199 Jiefang South Road, Xuzhou, 221000, Jiangsu, China

    Wenjing Du

  2. Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou, 221000, Jiangsu, China

    Yiquan Sang

  3. Department of Nephrology, Xuzhou Central Hospital, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou, 221000, Jiangsu, China

    Yun-Huan Bai

Authors
  1. Wenjing Du
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  2. Yiquan Sang
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  3. Yun-Huan Bai
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Contributions

WD participated in the study design and carried out the study; YS participated in collecting data and data analysis. Y-HB performed the statistical analysis and drafted the manuscript.

Corresponding author

Correspondence to Wenjing Du.

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Conflict of interest

Wenjing Du declares that he/she has no conflict of interest, Yiquan Sang declares that he/she has no conflict of interest, and Yun-Huan Bai declares that he/she has no conflict of interest.

Ethical approval

Protocols of the investigation were approved by the ethics committee of Xuzhou Central Hospital.

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Du, W., Sang, Y. & Bai, YH. LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1 alpha. Mol. Cell. Toxicol. 18, 419–429 (2022). https://doi.org/10.1007/s13273-021-00214-w

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  • DOI: https://doi.org/10.1007/s13273-021-00214-w

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