| First Author | Hayashi D | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 2597 |
| PubMed ID | 28572624 | Mgi Jnum | J:272093 |
| Mgi Id | MGI:6282544 | Doi | 10.1038/s41598-017-02354-3 |
| Citation | Hayashi D, et al. (2017) Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice. Sci Rep 7(1):2597 |
| abstractText | Diabetic nephropathy (DN) is one of vascular complications of diabetes and is caused by abnormal protein kinase C activation as a result of increased diacylglycerol (DG) production in diabetic hyperglycaemia. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. Therefore, it is expected that the activation of DGK would ameliorate DN. Indeed, it has been reported that vitamin E (VtE) ameliorates DN in rat by activating DGK, and we recently reported that VtE specifically activates DGKalpha isoform in vitro. However, whether DGKalpha is involved in the VtE-induced amelioration of DN in vivo remains unknown. Therefore, we investigated the VtE-induced amelioration of DN in wild-type (DGKalpha(+/+)) and DGKalpha-deficient (DGKalpha(-/-)) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGKalpha(+/+) mice but not in the DGKalpha(-/-) mice. Moreover, transmission electron microscopy of glomeruli and immunofluorescent staining of glomerular epithelial cells (podocytes) indicated that VtE ameliorates podocyte pathology and prevents podocyte loss in the DGKalpha(+/+) mice but not in the DGKalpha(-/-) mice. We showed that VtE can ameliorate DN in mice and that DGKalpha is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGKalpha is an attractive therapeutic target for DN. |
