Epigenetic modulation of autophagy genes linked to diabetic nephropathy by administration of isorhamnetin in Type 2 diabetes mellitus rats.
Marwa MatboliDoaa IbrahimAmany H HasaninMohamed K HassanEman K HabibMiram M BekhetAhmed M AfifiSanaa EissaPublished in: Epigenomics (2021)
Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes (FYCO1, ULK, TECPR1 and WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes. Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.
Keyphrases
- blood glucose
- glycemic control
- high fat diet
- diabetic nephropathy
- cell death
- gene expression
- endoplasmic reticulum stress
- dna methylation
- type diabetes
- oxidative stress
- signaling pathway
- insulin resistance
- genome wide
- cell proliferation
- diabetic rats
- long non coding rna
- adipose tissue
- blood pressure
- electron microscopy
- genome wide identification
- bioinformatics analysis
- long noncoding rna
- transcription factor
- high glucose
- mass spectrometry
- weight loss
- genome wide analysis
- binding protein
- endothelial cells
- cardiovascular risk factors
- wound healing
- protein protein
- liquid chromatography
- gestational age