| First Author | Mori J | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 306 |
| Issue | 8 | Pages | F812-21 |
| PubMed ID | 24553436 | Mgi Jnum | J:208413 |
| Mgi Id | MGI:5563274 | Doi | 10.1152/ajprenal.00655.2013 |
| Citation | Mori J, et al. (2014) Angiotensin 1-7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity. Am J Physiol Renal Physiol 306(8):F812-21 |
| abstractText | The renin-angiotensin system, especially angiotensin II (ANG II), plays a key role in the development and progression of diabetic nephropathy. ANG 1-7 has counteracting effects on ANG II and is known to exert beneficial effects on diabetic nephropathy. We studied the mechanism of ANG 1-7-induced beneficial effects on diabetic nephropathy in db/db mice. We administered ANG 1-7 (0.5 mg.kg(-1).day(-1)) or saline to 5-mo-old db/db mice for 28 days via implanted micro-osmotic pumps. ANG 1-7 treatment reduced kidney weight and ameliorated mesangial expansion and increased urinary albumin excretion, characteristic features of diabetic nephropathy, in db/db mice. ANG 1-7 decreased renal fibrosis in db/db mice, which correlated with dephosphorylation of the signal transducer and activator of transcription 3 (STAT3) pathway. ANG 1-7 treatment also suppressed the production of reactive oxygen species via attenuation of NADPH oxidase activity and reduced inflammation in perirenal adipose tissue. Furthermore, ANG 1-7 treatment decreased lipid accumulation in db/db kidneys, accompanied by increased expressions of renal adipose triglyceride lipase (ATGL). Alterations in ATGL expression correlated with increased SIRT1 expression and deacetylation of FOXO1. The upregulation of angiotensin-converting enzyme 2 levels in diabetic nephropathy was normalized by ANG 1-7. ANG 1-7 treatment exerts renoprotective effects on diabetic nephropathy, associated with reduction of oxidative stress, inflammation, fibrosis, and lipotoxicity. ANG 1-7 can represent a promising therapy for diabetic nephropathy. |
