Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ
In: Biochemical Journal, Jg. 432 (2010-10-25), S. 9-19
Online
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Zugriff:
Mitochondrial production of ROS (reactive oxygen species) is thought to be associated with the cellular damage resulting from chronic exposure to high glucose in long-term diabetic patients. We hypothesized that a mitochondria-targeted antioxidant would prevent kidney damage in the Ins2+/−AkitaJ mouse model (Akita mice) of Type 1 diabetes. To test this we orally administered a mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways were determined by immunohistochemical analysis, and mitochondria were isolated from the kidney for functional assessment. MitoQ treatment improved tubular and glomerular function in the Ins2+/−AkitaJ mice. MitoQ did not have a significant effect on plasma creatinine levels, but decreased urinary albumin levels to the same level as non-diabetic controls. Consistent with previous studies, renal mitochondrial function showed no significant change between any of the diabetic or wild-type groups. Importantly, interstitial fibrosis and glomerular damage were significantly reduced in the treated animals. The pro-fibrotic transcription factors phospho-Smad2/3 and β-catenin showed a nuclear accumulation in the Ins2+/−AkitaJ mice, which was prevented by MitoQ treatment. These results support the hypothesis that mitochondrially targeted therapies may be beneficial in the treatment of diabetic nephropathy. They also highlight a relatively unexplored aspect of mitochondrial ROS signalling in the control of fibrosis.
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Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ
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Autor/in / Beteiligte Person: | Agarwal, Anupam ; Chacko, Balu K. ; Zinn, Kurt R. ; Srivastava, Anup ; Kalyanaraman, Balaraman ; Ye, Yaozu ; Johnson, Michelle S. ; Ulasova, Elena ; Murphy, Michael P. ; Reily, Colin ; Darley-Usmar, Victor M. |
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Zeitschrift: | Biochemical Journal, Jg. 432 (2010-10-25), S. 9-19 |
Veröffentlichung: | Portland Press Ltd., 2010 |
Medientyp: | unknown |
ISSN: | 1470-8728 (print) ; 0264-6021 (print) |
DOI: | 10.1042/bj20100308 |
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