Metformin ameliorates the severity of experimental Alport syndrome

Kohei Omachi, Shota Kaseda, Tsubasa Yokota, Misato Kamura, Keisuke Teramoto, Jun Kuwazuru, Haruka Kojima, Hirofumi Nohara, Kosuke Koyama, Sumio Ohtsuki, Shogo Misumi, Toru Takeo, Naomi Nakagata, Jian Dong Li, Tsuyoshi Shuto, Mary Ann Suico, Jeffrey H. Miner, Hirofumi Kai

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article number7053
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

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