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Tripartite motif containing 23 functions as a critical regulator in macrophages to control the pathological feature of diabetic nephropathy

  • Nephrology - Original Paper
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Abstract

Background

Diabetic nephropathy (DN) is a kidney disease resulting from diabetes. Macrophages and macrophage-mediated inflammation contributed to the development of DN. Tripartite motif containing 23 (TRIM23) is E3 ligase and has been involved in inflammation. Until now, the precise roles of TRIM23 in DN are not described yet. Therefore, we evaluated the functions of TRIM23 in DN.

Methods

We generated mice with TRIM23 deficiency in macrophages. We also established diabetic mice model. The expression of TRIM23 was measured in diabetic animals. The DN symptoms were compared between diabetic wild-type (WT) mice and TRIM23 conditional knock out mice. The cytokine expression, ubiquitination of TAB2, and interactions between TAB2 and IKK were compared in oxidized low-density lipoprotein (oxLDL) or lipopolysaccharides (LPS)-treated WT and TRIM23-deficient macrophages.

Results

Upregulation of TRIM23 was observed in diabetic mice and LPS or oxLDL-treated macrophages. Diabetic mice with TRIM23 deficiency in macrophages had attenuated DN symptoms. TRIM23-deficient macrophages had decreased pro-inflammatory cytokines production after oxLDL or LPS stimulation. TRIM23 was predicted to interact with TAB2. The ubiquitination of TAB2 was abolished in oxLDL-treated TRIM23-deficient macrophages, which correlated with decreased activation of IKK.

Conclusion

TRIM23 regulates inflammation in macrophages and plays important role in DN.

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Data availability

Data could be obtained upon reasonable request to the corresponding author.

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Funding

This project was funded by Health Scientific project of Heilongjiang Province (2020–372).

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    1. Department of Endocrinology, Daqing Oilfield General Hospital, No. 9, Zhongkang Street, Sartu District, Daqing, 163000, Heilongjiang, China

      Wei Quan & Lin Wang

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    1. Wei Quan
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    Quan, W., Wang, L. Tripartite motif containing 23 functions as a critical regulator in macrophages to control the pathological feature of diabetic nephropathy. Int Urol Nephrol 55, 1263–1270 (2023). https://doi.org/10.1007/s11255-022-03419-7

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