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Baicalin reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal injury in type 1 diabetic mouse model
- Source :
- Cell Cycle
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- Baicalin is a flavone glycoside that possesses numerous pharmacological properties. but its protective mode of action in kidney injury induced by diabetes mellitus remains incompletely understood. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin could ameliorate diabetes-induced the pathological changes of the kidney function and morphology through suppressing inflammation and oxidative stress. Furthermore, baicalin treatment could alleviate interstitial fibrosis in the diabetic kidney via inhibiting epithelial-to-mesenchymal transition (EMT), which was accompanied by a sharp upregulation of Klotho, the endogenous inhibitor of renal fibrosis. We further verified that baicalin-rescued expression of Klotho was associated with Klotho promoter hypomethylation due to aberrant methyltransferase 3a expressions. Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Baicalin in HK2 cells. These findings suggested that baicalin could alleviate renal injury-induced by diabates through partly modulating Klotho promoter methylation, which provides new insights into the treatment of diabetic nephropathy.
- Subjects :
- 0301 basic medicine
Biology
urologic and male genital diseases
Diabetes Mellitus, Experimental
Diabetic nephropathy
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Downregulation and upregulation
Fibrosis
medicine
Renal fibrosis
Animals
Molecular Biology
Klotho
Klotho Proteins
Glucuronidase
Flavonoids
Kidney
Cell Biology
Acute Kidney Injury
DNA Methylation
Streptozotocin
medicine.disease
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Diabetes Mellitus, Type 1
chemistry
030220 oncology & carcinogenesis
Cancer research
Female
Baicalin
Developmental Biology
medicine.drug
Research Paper
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell Cycle
- Accession number :
- edsair.doi.dedup.....738edf9c981d091edd399a50acaaf834
- Full Text :
- https://doi.org/10.6084/m9.figshare.13241009