Metformin ameliorates the severity of experimental Alport syndrome
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...
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2021
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oai:doaj.org-article:d6c03b25c7634eeda9e0874c08df981e2021-12-02T13:27:08ZMetformin ameliorates the severity of experimental Alport syndrome10.1038/s41598-021-86109-12045-2322https://doaj.org/article/d6c03b25c7634eeda9e0874c08df981e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86109-1https://doaj.org/toc/2045-2322Abstract 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.Kohei OmachiShota KasedaTsubasa YokotaMisato KamuraKeisuke TeramotoJun KuwazuruHaruka KojimaHirofumi NoharaKosuke KoyamaSumio OhtsukiShogo MisumiToru TakeoNaomi NakagataJian-Dong LiTsuyoshi ShutoMary Ann SuicoJeffrey H. MinerHirofumi KaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
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Medicine R Science Q 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 Metformin ameliorates the severity of experimental Alport syndrome |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Kohei Omachi |
| title |
Metformin ameliorates the severity of experimental Alport syndrome |
| title_short |
Metformin ameliorates the severity of experimental Alport syndrome |
| title_full |
Metformin ameliorates the severity of experimental Alport syndrome |
| title_fullStr |
Metformin ameliorates the severity of experimental Alport syndrome |
| title_full_unstemmed |
Metformin ameliorates the severity of experimental Alport syndrome |
| title_sort |
metformin ameliorates the severity of experimental alport syndrome |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/d6c03b25c7634eeda9e0874c08df981e |
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