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Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression
Linxi Lv1, Hui Jiang1, Dianze Song1,2,3
1Institute of Rheumatology and Immunology, the Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Road, Nanchong, 637001, Sichuan, China.
Arthritis Research & Therapy
|July 19, 2023
Summary
Sirtuin 3 (Sirt3) deficiency worsens inflammation from monosodium urate (MSU) crystals. Sirt3 alleviates this inflammation by suppressing Acod1 expression, offering a potential therapeutic target for gout.
Area of Science:
- Immunology
- Metabolism
- Molecular Biology
Background:
- Sirtuin 3 (Sirt3) deficiency is linked to inflammatory conditions.
- Monosodium urate (MSU) crystals trigger inflammatory responses relevant to gout.
Purpose of the Study:
- Investigate Sirt3's role in MSU crystal-induced inflammation.
- Elucidate the molecular mechanisms underlying Sirt3's function in this inflammatory process.
Main Methods:
- Measured Sirt3 expression in gout patients' peripheral blood mononuclear cells (PBMCs).
- Utilized bone marrow-derived macrophages (BMDMs), C57BL/6, and Sirt3 knockout mice for functional studies.
- Employed RNA sequencing, bioinformatics, RT-PCR, and Western blot analyses.
Main Results:
- Sirt3 expression was reduced in gout patients' PBMCs.
- Sirt3 activation decreased acetylation of mitochondrial proteins, including SOD2.
- Sirt3 suppressed Acod1 (Irg1) expression, which promotes inflammation.
- Acod1 knockdown reduced mitochondrial reactive oxygen species (mtROS), macrophage migration, and mitochondrial fragmentation.
- Acod1 overexpression impacted tricarboxylic acid (TCA) cycle intermediates but not itaconic acid levels.
- Sirt3 deficiency exacerbated MSU crystal-induced inflammation in vitro and in vivo.
Conclusions:
- Sirt3 plays a protective role against MSU crystal-induced inflammation.
- Sirt3 alleviates inflammation by inhibiting Acod1 expression.
- Targeting Sirt3 or Acod1 may offer therapeutic strategies for gout.
