| Title | 5-Hydroxymethylcytosine profiles in plasma cell-free DNA reflect molecular characteristics of diabetic kidney disease |
| Authors | Chu, Jin-Lin Bi, Shu-Hong He, Yao Ma, Rui-Yao Wan, Xing-Yu Wang, Zi-Hao Zhang, Lei Zheng, Meng-Zhu Yang, Zhan-Qun Du, Ling-Wei Maimaiti, Yiminiguli Biekedawulaiti, Gulinazi Duolikun, Maimaitiyasen Chen, Hang-Yu Chen, Long Li, Lin-Lin Tie, Lu Lin, Jian |
| Affiliation | Xinjiang Med Univ, Coll Pharm, Key Lab Act Components Xinjiang Nat Med & Drug Rel, Urumqi, Peoples R China State Key Lab Pathogenesis, Prevent & Treatment High Incidence Dis Cent Asia, Urumqi, Peoples R China Peking Univ Third Hosp, Dept Nephrol, Beijing, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing Key Laboratory of Tumor Systems Biology, Beijing, Peoples R China Peking Univ Third Hosp, Dept Pharm, Beijing, Peoples R China Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Innovat Ctr Genom,Key Lab Bioorgan Chem & Mol Engn, Beijing, Peoples R China Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China Hainan Univ, Sch Food Sci & Engn, Haikou, Peoples R China |
| Keywords | ADHESION INFLAMMATION NEPHROPATHY SIGNATURES |
| Issue Date | 29-Jul-2022 |
| Publisher | FRONTIERS IN ENDOCRINOLOGY |
| Abstract | BackgroundDiabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions. MethodsWe utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database. ResultsThis study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1). ConclusionsThe 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD. |
| URI | http://hdl.handle.net/20.500.11897/652447 |
| ISSN | 1664-2392 |
| DOI | 10.3389/fendo.2022.910907 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 基础医学院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ 生物有机与分子工程教育部重点实验室 |
