DNA methylation and whole-genome transcription analysis in CD4+ T cells from systemic lupus erythematosus patients with or without renal damage

被引：4

作者：

Liu, Xiaomin ^{[1
]}

Zhou, Siyu ^{[2
]}

Huang, Mengjie ^{[1
]}

Zhao, Ming ^{[2
]}

Zhang, Weiguang ^{[1
]}

Liu, Qun ^{[1
]}

Song, Kangkang ^{[1
,3
]}

Wang, Xu ^{[1
]}

Liu, Jiaona ^{[1
]}

Qing, Ouyang ^{[1
]}

Dong, Zheyi ^{[1
]}

Yang, Ming ^{[2
]}

Li, Zhenzhen ^{[1
]}

Lin, Li ^{[1
]}

Liu, Yi ^{[4
]}

Yu, Yang ^{[4
]}

Liao, Simin ^{[5
]}

Zhu, Jian ^{[5
]}

Liu, Lin ^{[6
]}

Li, Wenge ^{[6
]}

Jia, Linpei ^{[7
]}

Zhang, Aihua ^{[7
]}

Guo, Chaomin ^{[8
]}

Yang, Liuyang ^{[7
]}

Li, Qing gang ^{[1
]}

Bai, Xueyuan ^{[1
]}

Li, Ping ^{[1
]}

Cai, Guangyan ^{[1
]}

Lu, Qianjin ^{[2
,9
]}

Chen, Xiangmei ^{[1
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Gen Hosp Peoples Liberat Army, Natl Clin Res Ctr Kidney Dis, Hosp 301,Dept Nephrol,Natl Clin Res Ctr Kidney Dis, 28 Fuxing Rd Beijing wukesong, Beijing 100853, Peoples R China

[2] Cent South Univ, Dept Dermatol, Hunan Key Lab Med Epigen, Xiangya Hosp 2, Changsha, Peoples R China

[3] Capital Med Univ, Beijing Tongren Hosp, Dept Nephrol, Beijing, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Blood Transfus, Beijing, Peoples R China

[5] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Rheumatol & Immunol, Beijing, Peoples R China

[6] China Japan Friendship Hosp, Dept Nephrol, Beijing, Peoples R China

[7] Capital Med Univ, Xuanwu Hosp, Dept Nephrol, Beijing, Peoples R China

[8] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Lab Med Dept, Beijing, Peoples R China

[9] Chinese Acad Med Sci & Peking Union Med Coll, Inst Dermatol, Chinese Acad Med Sci, Key Lab Basic & Translat Res Immune Mediated Skin, 12 Jiangwangmiao St, Nanjing 210042, Peoples R China

来源：

CLINICAL EPIGENETICS | 2024年 / 16卷 / 01期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

LN; CD4(+) T cell; DNA methylation; MESSENGER-RNA; EXPRESSION; CLASSIFICATION; EPIGENETICS; DISEASES; GENE;

D O I：

10.1186/s13148-024-01699-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：13

共 52 条

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