Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney

Abstract Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly ass...

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Main Authors: Yongwei Jiang, GuoXiong Deng, Chengyin Liu, Han Tang, Jing Zheng, Xiaomu Kong, Meimei Zhao, Yi Liu, Peng Gao, Tianbao Li, Hailing Zhao, Yongtong Cao, Ping Li, Liang Ma
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Clinical Epigenetics
Subjects:
Online Access:https://doi.org/10.1186/s13148-023-01620-8
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author Yongwei Jiang
GuoXiong Deng
Chengyin Liu
Han Tang
Jing Zheng
Xiaomu Kong
Meimei Zhao
Yi Liu
Peng Gao
Tianbao Li
Hailing Zhao
Yongtong Cao
Ping Li
Liang Ma
author_facet Yongwei Jiang
GuoXiong Deng
Chengyin Liu
Han Tang
Jing Zheng
Xiaomu Kong
Meimei Zhao
Yi Liu
Peng Gao
Tianbao Li
Hailing Zhao
Yongtong Cao
Ping Li
Liang Ma
author_sort Yongwei Jiang
collection DOAJ
description Abstract Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels 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 landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.
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spelling doaj.art-94bfd5649024458a81592fcc774f2dd32024-01-07T12:31:17ZengBMCClinical Epigenetics1868-70832024-01-0116111010.1186/s13148-023-01620-8Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidneyYongwei Jiang0GuoXiong Deng1Chengyin Liu2Han Tang3Jing Zheng4Xiaomu Kong5Meimei Zhao6Yi Liu7Peng Gao8Tianbao Li9Hailing Zhao10Yongtong Cao11Ping Li12Liang Ma13Clinical Laboratory, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalBioChain (Beijing) Science and Technology Inc.BioChain (Beijing) Science and Technology Inc.Clinical Laboratory, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalBioChain (Beijing) Science and Technology Inc.Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Science, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Science, China-Japan Friendship HospitalClinical Laboratory, China-Japan Friendship HospitalAbstract Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels 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 landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.https://doi.org/10.1186/s13148-023-01620-8Hyper-methionineDiabetic nephropathyDifferential methylation profilesTangshen formulaMethylation patterns
spellingShingle Yongwei Jiang
GuoXiong Deng
Chengyin Liu
Han Tang
Jing Zheng
Xiaomu Kong
Meimei Zhao
Yi Liu
Peng Gao
Tianbao Li
Hailing Zhao
Yongtong Cao
Ping Li
Liang Ma
Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
Clinical Epigenetics
Hyper-methionine
Diabetic nephropathy
Differential methylation profiles
Tangshen formula
Methylation patterns
title Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
title_full Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
title_fullStr Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
title_full_unstemmed Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
title_short Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney
title_sort tangshen formula improves diabetic nephropathy in stz induced diabetes rats fed with hyper methionine by regulating the methylation status of kidney
topic Hyper-methionine
Diabetic nephropathy
Differential methylation profiles
Tangshen formula
Methylation patterns
url https://doi.org/10.1186/s13148-023-01620-8
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