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Overexpression of TRIM3 protects against LPS-induced acute kidney injury via repressing IRF3 pathway and NLRP3 inflammasome

  • Nephrology - Original Paper
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Abstract

Purpose

The pathological process of sepsis involves multiple system organs, including kidney. Sepsis-induced acute kidney injury (AKI) has high morbidity and high mortality. Overproduced inflammatory factors contribute to the occurrence and evolvement of AKI. Here, the role and underlying mechanism of tripartite motif containing 3 (TRIM3) and in AKI was explored.

Methods

Lipopolysaccharide (LPS) was used for constructing AKI model both in vitro and in vivo. RT-PCR and western blot were performed to detect TRIM3, Interferon regulatory factor 3 (IRF3) and NLRP3-ASC-Caspase1 inflammasome. Upon selectively regulating the TRIM3 or IRF3 expression, the proliferation, apoptosis and inflammatory response were detected. The interaction between TRIM3 and IRF3 was verified by Immunoprecipitation (IP).

Results

TRIM3 was down-regulated in mediated injury renal tubular epithelial cell line HK-2 treated with LPS. Overexpression of TRIM3 promoted cell viability and reduced apoptosis. In addition, overexpression of TRIM3 inhibited the expression of inflammatory factors (IL-1β, IL-6, TNF-α and IL-18), dampened the phosphorylation of IRF3 and repressed NLRP3 inflammasome activation. Furthermore, TRIM3 overexpression significantly eased the LPS-induced damage on AKI rat model and decreased the serum creatinine and urea nitrogen levels in rat kidney tissues. The results of immunohistochemistry (IHC) and Western blot manifested that TRIM3 was increased dramatically after TRIM3 was overexpressed in the rat kidney tissues, while IRF3 and NLRP3-ASC-Caspase1 inflammasome were significantly repressed following TRIM3 upregulation in the kidney tissues. Mechanistically, TRIM3 interacted with IRF3 and inhibited its phosphorylation.

Conclusion

Overexpression of TRIM3 protected against LPS-induced AKI by inhibiting the IRF3 pathway and NLRP3 inflammasome activation.

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Data availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. The Central Hospital of ENSHI TUJIA AND MIAO Autonomous Prefecture, 158 Wuyang County Street, Enshi City, 445000, Hubei, China

    Weiwei Li, Yunzhi Tan, Feng Gao & Miaomiao Xiang

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  1. Weiwei Li
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  2. Yunzhi Tan
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  3. Feng Gao
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  4. Miaomiao Xiang
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Contributions

Conceived and designed the experiments: FG; performed the experiments: WL; statistical analysis: YT, MX; wrote the paper: WL. All authors read and approved the final manuscript.

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Correspondence to Feng Gao.

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The authors declare that they have no competing interests.

Ethical approval

Our study was approved by the Animal Ethics Committee of the central hospital of ENSHI TUJIA AND MIAO autonomous prefecture.

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Li, W., Tan, Y., Gao, F. et al. Overexpression of TRIM3 protects against LPS-induced acute kidney injury via repressing IRF3 pathway and NLRP3 inflammasome. Int Urol Nephrol 54, 1331–1342 (2022). https://doi.org/10.1007/s11255-021-03017-z

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  • DOI: https://doi.org/10.1007/s11255-021-03017-z

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