Defective fatty acid oxidation in renal tubular epithelial cells plays a key role in kidney fibrosis development
By H. Kang, S. Ahn, Peter Choi, Y. Ko, S. Han, Frank Chinga, Ae Seo Deok Park, Jianling Tao, K. Sharma, J. Pullman and 3 more. Nature Medicine, 2014
1,352 citations recorded by the source corpus.
Renal fibrosis is the histological manifestation of a progressive, usually irreversible process causing chronic and end-stage kidney disease. We performed genome-wide transcriptome studies of a large cohort (n = 95) of normal and fibrotic human kidney tubule samples followed by systems and network analyses and identified inflammation and metabolism as the top dysregulated pathways in the diseased kidneys. In particular, we found that humans and mouse models with tubulointerstitial fibrosis had lower expression of key enzymes and regulators of fatty acid oxidation (FAO) and higher intracellular lipid deposition compared to controls. In vitro experiments indicated that inhibition of FAO in tubule epithelial cells caused ATP depletion, cell death, dedifferentiation and intracellular lipid deposition, phenotypes observed in fibrosis. In contrast, restoring fatty acid metabolism by genetic or pharmacological methods protected mice from tubulointerstitial fibrosis. Our results raise the possibility that correcting the metabolic defect in FAO may be useful for preventing and treating chronic kidney disease.
Subfields: Nephrology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/2899531879b24b6dbc534dea2a19ee108ac4bbc4
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Nephrology
In Pulmonary and Respiratory Medicine
Citations in the corpus
- The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders. (2016, background): “In humans and mouse models, decreased FAO contributes to the development of kidney fibrosis (43).”
- Renal tubule injury: a driving force toward chronic kidney disease. (2018, background): “Further investigation demonstrated that TGF-b1 inhibits the expression of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme in fatty acid oxidation, and thereby decreases fatty acid metabolism.(214) miR-21 has been shown to regulate the metabolic pathways.”