| First Author | Muraoka H | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 1 | Pages | 199-212.e5 |
| PubMed ID | 30943401 | Mgi Jnum | J:280488 |
| Mgi Id | MGI:6368895 | Doi | 10.1016/j.celrep.2019.03.024 |
| Citation | Muraoka H, et al. (2019) Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy. Cell Rep 27(1):199-212.e5 |
| abstractText | Nicotinamide adenine dinucleotide (NAD(+)) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD(+) precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy. The expression of Nampt in PTs was downregulated in streptozotocin (STZ)-treated diabetic mice when they exhibited albuminuria. This albuminuria was ameliorated in PT-specific Nampt-overexpressing transgenic (TG) mice. PT-specific Nampt-conditional knockout (Nampt CKO) mice exhibited TBM thickening and collagen deposition, which were associated with the upregulation of the profibrogenic gene TIMP-1. Nampt CKO mice also exhibited the downregulation of sirtuins, particularly in Sirt6. PT-specific Sirt6-knockout mice exhibited enhanced fibrotic phenotype resembling that of Nampt CKO mice with increased Timp1 expression. In conclusion, the Nampt-Sirt6 axis in PTs serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. |
