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Selective deficiency of UCP-1 and adropin may lead to different subtypes of anti-neutrophil cytoplasmic antibody-associated vasculitis

Genes & Immunity volume 24, pages 39–45 (2023)Cite this article

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Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that is prone to respiratory and renal failures. Its major target antigens are serine protease 3 (PR3) and myeloperoxidase (MPO), but the determinants of PR3 and MPO subtypes are still unclear. Uncoupling protein-1 (UCP-1) and adropin (Adr) regulate mutually and play an important role in endothelial cell injury. In this study, adropin and UCP-1 knockout (AdrKO and UCP-1-KO) models were established on the basis of C57BL/6 J mice. The results showed that UCP-1-KO and AdrKO mice similar to AAV: significant inflammatory cell infiltration, vascular wall damage, and erythrocyte extravasation. The pathological basis of AdrKO was that endothelial cells adhered and activated neutrophils to release MPO, and the core gene was peroxisome proliferator–activated receptor gamma (PPARG). However, UCP-1-KO induced PR3 release, and the accumulation and expression of tissue factor on the vascular wall, and the core gene was peroxisome proliferator–activated receptor delta (PPARD). The present study verified that the subtypes of AAV may be genetically different diseases and it also provide novel experimental evidence for clinical differentiation of the two subtypes.

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Fig. 1: Mechanism map.
Fig. 2: Differences in the inflammatory models induced by AdrKO and UCP-1-KO.
Fig. 3: Differences in pathological tissues between AdrKO and UCP-1-KO.
Fig. 4: Regulatory network between AdrKO and UCP-1-KO.

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Data availability

The data used to support the findings of this study are currently under embargo while the research findings are commercialized. Requests for data, [12 months] after publication of this article, will be considered by the corresponding author.

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Funding

This work was supported by Fujian Natural Science Foundation (No. 2021J02036). These funding sources played key supportive role for sample collection, molecular analysis of patient samples, bioinformatics analysis.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Medical Technology and Engineering College, Fujian Medical University, Fuzhou, 350005, China

    Qingquan Chen

  2. Department of Reproductive Medicine, The First Affiliated Hospital, Xiamen University, Xiamen, 361005, Fujian, China

    Youzhu Li

  3. Center of Reproductive Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China

    Xinxin Guo, Yuxin Liu, Yujia Guo & Qicai Liu

  4. Department of Respiratory and Critical Care Medicine, Research Laboratory of the Respiratory System Diseases, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China

    Xiaoting Lv

  5. Division of Neonatology, Fujian Maternal and Child Health Hospital, Fujian Medical University, Fuzhou, 350001, China

    Yunfeng Lin

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Contributions

Q-CL planned the project. Q-CL, and Q-QC conceived of and designed the study. Q-CL, X-TL, Y-JG, Y-FL and X-XG performed the sample collection. Y-ZL, Q-CL, and Y-FL performed the expression analysis. Q-CL, and Y-FL analyzed the data and drafted the manuscript. All authors reviewed the manuscript and approved the final version.

Corresponding authors

Correspondence to Yunfeng Lin or Qicai Liu.

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The authors declare no competing interests.

Ethical approval and consent to participate

The data collection scheme and research carried out were approved by the Medical ethics committee of the First Affiliated Hospital of Fujian Medical University. The protocol was approved by the Medical ethics committee of the First Affiliated Hospital of Fujian Medical University.

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Chen, Q., Li, Y., Guo, X. et al. Selective deficiency of UCP-1 and adropin may lead to different subtypes of anti-neutrophil cytoplasmic antibody-associated vasculitis. Genes Immun 24, 39–45 (2023). https://doi.org/10.1038/s41435-023-00195-x

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