Affiliation:
1. China-Japan Friendship Hospital
2. BioChain (Beijing) Science & Technology Inc.
Abstract
Abstract
This study aimed to investigate the impact of hyper-methionine (HM) feeding on diabetic nephropathy (DN) pathogenesis by examining and analyzing differential methylation profiles. Eight-week-old male Wistar rats (250–300g) were randomly divided into four groups: control group (healthy, n = 8), streptozocin (STZ) induced DN rats (STZ group, n = 8), STZ-induced DN rats fed with HM (STZ + HM group, n = 8), and the Tangshen Formula (TSF) treatment for STZ + HM rats (TSF group, n = 8). Blood glucose and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation profiles were analyzed using reduced representative bisulfite sequencing (RRBS).The STZ group and STZ + HM group exhibited increased levels of blood glucose and urinary albumin/creatinine compared to control group. STZ + HM group showed significantly higher levels of urinary albumin/creatinine (411.90 ± 88.86 mg/g) than the STZ group (238.41 ± 62.52 mg/g). A total of 71,957 differentially methylated regions (DMRs) were identified, with 48,950 (68.02%) being hyper-methylated and 23,007 (31.98%) being hypo-methylated. In-depth analysis of DNA methylation profiles revealed 19 genes, out of 797 methylated genes associated with DN. HM exacerbates DN through altered methylation patterns at specific CpG sites. TSF group demonstrated significant reductions in glucose and urinary albumin/creatinine levels compared to the STZ + HM group. Furthermore, TSF shows potential as an effective treatment for DN by restoring aberrant methylation levels. The identification of specific genes associated with DN provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.
Publisher
Research Square Platform LLC
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