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Cited by 204Chronic Kidney Disease and DiabetesMitochondrial Function and PathologyRenal Diseases and Glomerulopathies

Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ

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Chacko, Balu K., Reily, Colin, Srivastava, Anup, Johnson, Michelle S., Ye, Yaozu, Ulasova, Elena, Agarwal, Anupam, Zinn, Kurt R. +3 more·2010·Biochemical Journal
DOI 10.1042/bj20100308PMC PMC2973231
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Abstract

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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  • MitoQ has been tested successfully in human diseases such as Hepatitis C induced liver disease and skin photo damage and in experimental animal models including ischemia-reperfusion, neurodegenerative diseases, diabetes, and alcohol-induced hepatosteatosis.

    “For example, Mitoquinone (MitoQ) has been tested successfully in human diseases such as Hepatitis C induced liver disease and skin photo damage as well as a number of experimental animal models including ischemia-reperfusion, neurodegenerative diseases, diabetes, and alcohol-induced hepatosteatosis [8–14].”

    From Mitochondrially targeted compounds and their impact on cellular bioenergetics (2013) · cites this paper as [13]

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Authors
Chacko, B. K., Reily, C., Srivastava, A., Johnson, M. S., Ye, Y., Ulasova, E., Agarwal, A., Zinn, K. R., Murphy, M. P., Kalyanaraman, B., & Darley-Usmar, V.
Affiliations
  • University of Alabama at Birmingham (US)
  • MRC Mitochondrial Biology Unit (GB)
  • Medical College of Wisconsin (US)
Corresponding author
  • Reily, Colin
  • Srivastava, Anup
  • Ye, Yaozu
  • Ulasova, Elena
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2010-10-25
Volume
432
Issue
1
Pages
9-19
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj20100308
PMC
PMC2973231
OpenAlex
W2050979875
Cited by
204
References
5
Citations by year
2026: 1 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 16 · 2019: 13 · 2018: 16 · 2017: 13 · 2016: 13 · 2015: 20 · 2014: 13 · 2013: 23 · 2012: 21
FWCI
14.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Journal (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • University of California, San Diego
  • National Cancer Institute (P30CA013148)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK079337, R01DK075865, DK-075865, P30DK079337, R56DK075865)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords
diabetic nephropathy, MitoQ, mitochondria-targeted antioxidants, type 1 diabetes, renal fibrosis, glomerular injury, mitochondrial reactive oxygen species, Smad2/3 signaling, β-catenin, coenzyme Q10, tubular function, urinary albumin
MeSH terms
Animals, Blood Glucose, Cell Nucleus, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Fibrosis, Glomerular Mesangium, Immunohistochemistry, Insulin, Kidney, Kidney Tubules, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Microscopy, Electron, Mitochondria, Phosphorylation, Ubiquinone, beta Catenin, Mice, Smad2 Protein, Smad3 Protein

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