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Metformin ameliorates the severity of experimental Alport syndrome
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021), Scientific Reports
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Metformin is widely used for the treatment of type 2 diabetes, and increasing numbers of studies have shown that metformin also ameliorates tumor progression, inflammatory disease, and fibrosis. However, the ability of metformin to improve non-diabetic glomerular disease and chronic kidney disease (CKD) has not been explored. To investigate the effect of metformin on non-diabetic glomerular disease, we used a mouse model of Alport syndrome (Col4a5 G5X) which were treated with metformin or losartan, used as a control treatment. We also investigated the effect of metformin on adriamycin-induced glomerulosclerosis model. Pathological and biochemical analysis showed that metformin or losartan suppressed proteinuria, renal inflammation, fibrosis, and glomerular injury and extended the lifespan in Alport syndrome mice. Transcriptome analysis showed that metformin and losartan influenced molecular pathways-related to metabolism and inflammation. Metformin altered multiple genes including metabolic genes not affected by losartan. Metformin also suppressed proteinuria and glomerular injury in the adriamycin-induced glomerulosclerosis mouse model. Our results showed that metformin ameliorates the glomerular sclerosis and CKD phenotype in non-diabetic chronic glomerular diseases. Metformin may have therapeutic potential for not only diabetic nephropathy but also non-diabetic glomerular disease including Alport syndrome.
- Subjects :
- 0301 basic medicine
endocrine system diseases
030232 urology & nephrology
Nephritis, Hereditary
Glomerular diseases
Type 2 diabetes
Kidney
urologic and male genital diseases
Severity of Illness Index
Diabetic nephropathy
Mice
0302 clinical medicine
Chronic kidney disease
Diabetic Nephropathies
Multidisciplinary
Proteinuria
digestive, oral, and skin physiology
Metformin
female genital diseases and pregnancy complications
Phenotype
Losartan
Nephrology
Medicine
medicine.symptom
Signal Transduction
medicine.drug
Collagen Type IV
medicine.medical_specialty
Science
Article
03 medical and health sciences
Internal medicine
medicine
Animals
Hypoglycemic Agents
Alport syndrome
business.industry
Glomerulosclerosis
nutritional and metabolic diseases
medicine.disease
Disease Models, Animal
030104 developmental biology
Endocrinology
Transcriptome
business
Kidney disease
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....80b89f186792b71383e279a761741580