We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Transgenic expression of proximal tubule peroxisome proliferator–activated receptor-α in mice confers protection during acute kidney injury.
- Authors
Shenyang Li; Nagothu, Kiran K.; Desai, Varsha; Taewon Lee; Branham, William; Moland, Carrie; Megyesi, Judit K.; Crew, Mark D.; Portilla, Didier
- Abstract
Our previous studies suggest that peroxisome proliferator–activated receptor-α (PPARα) plays a critical role in regulating fatty acid β-oxidation in kidney tissue and this directly correlated with preservation of kidney morphology and function during acute kidney injury. To further study this, we generated transgenic mice expressing PPARα in the proximal tubule under the control of the promoter of KAP2 (kidney androgen-regulated protein 2). Segment-specific upregulation of PPARα expression by testosterone treatment of female transgenic mice improved kidney function during cisplatin or ischemia–reperfusion-induced acute kidney injury. Ischemia–reperfusion injury or treatment with cisplatin in wild-type mice caused inhibition of fatty-acid oxidation, reduction of mitochondrial genes of oxidative phosphorylation, mitochondrial DNA, fatty-acid metabolism, and the tricarboxylic acid cycle. Similar injury in testosterone-treated transgenic mice resulted in amelioration of these effects. Similarly, there were increases in the levels of 4-hydroxy-2-hexenal-derived lipid peroxidation products in wild-type mice, which were also reduced in the transgenic mice. Similarly, necrosis of the S3 segment was reduced in the two injury models in transgenic mice compared to wild type. Our results suggest proximal tubule PPARα activity serves as a metabolic sensor. Its increased expression without the use of an exogenous PPARα ligand in the transgenic mice is sufficient to protect kidney function and morphology, and to prevent abnormalities in lipid metabolism associated with acute kidney injury.
- Subjects
PEROXISOMAL disorders; KIDNEY diseases; TRANSGENIC mice; CISPLATIN; KIDNEY necrosis; DISEASES
- Publication
Kidney International, 2009, Vol 76, Issue 10, p1049
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2009.330