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Magnesium isoglycyrrhizinate ameliorates fructose-induced podocyte apoptosis through downregulation of miR-193a to increase WT1
- Source :
- Biochemical pharmacology. 166
- Publication Year :
- 2019
-
Abstract
- High fructose intake is a risk of glomerular podocyte dysfunction. Podocyte apoptosis has emerged as a major cause of podocyte loss, exacerbating proteinuria. Magnesium isoglycyrrhizinate (MgIG) is usually used as a hepatoprotective agent in clinic. Liver and kidney injury often occurs in human diseases. Recent report shows that MgIG improves kidney function. In this study, we found that MgIG significantly alleviated kidney dysfunction, proteinuria and podocyte injury in fructose-fed rats. It also restored fructose-induced podocyte apoptosis in rat glomeruli and cultured differentiated podocytes. Of note, high-expression of miR-193a, downregulation of Wilms' tumor protein (WT1) and RelA, as well as upregulation of C-Maf inducing protein (C-mip) were observed in these animal and cell models. The data from the transfection of miR-193a mimic, miR-193a inhibitor, WT1 siRNA or LV5-WT1 in cultured differentiated podocytes showed that fructose increased miR-193a to down-regulate WT1, and subsequently activated C-mip to suppress RelA, causing podocyte apoptosis. These disturbances were significantly attenuated by MgIG. Taken together, these results provide the first evidence that MgIG restrains fructose-induced podocyte apoptosis at least partly through inhibiting miR-193a to upregulate WT1, supporting the application of MgIG with a novel mechanism-of-action against podocyte apoptosis associated with fructose-induced kidney dysfunction.
- Subjects :
- 0301 basic medicine
Male
Cell
Renal function
Apoptosis
Fructose
urologic and male genital diseases
Biochemistry
Podocyte
Cell Line
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
medicine
Animals
Humans
Hepatoprotective Agent
WT1 Proteins
Pharmacology
Proteinuria
Dose-Response Relationship, Drug
urogenital system
business.industry
Podocytes
Transfection
Saponins
Triterpenes
Rats
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Cancer research
medicine.symptom
business
Drugs, Chinese Herbal
Subjects
Details
- ISSN :
- 18732968
- Volume :
- 166
- Database :
- OpenAIRE
- Journal :
- Biochemical pharmacology
- Accession number :
- edsair.doi.dedup.....fa8c160a68605e89ef3c0c83bfdcca97