| Autor: |
Xiaomin Liu, Siyu Zhou, Mengjie Huang, Ming Zhao, Weiguang Zhang, Qun Liu, Kangkang Song, Xu Wang, Jiaona Liu, Qing OuYang, Zheyi Dong, Ming Yang, Zhenzhen Li, Li Lin, Yi Liu, Yang Yu, Simin Liao, Jian Zhu, Lin Liu, Wenge Li, Linpei Jia, Aihua Zhang, Chaomin Guo, LiuYang Yang, Qing gang Li, Xueyuan Bai, Ping Li, Guangyan Cai, Qianjin Lu, Xiangmei Chen |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Clinical Epigenetics, Vol 16, Iss 1, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1868-7083 |
| DOI: |
10.1186/s13148-024-01699-7 |
| Popis: |
Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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