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Publication

Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development.

Authors Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K Submitted By Katalin Susztak on 12/10/2014 Status Published Journal Nature medicine Year 2014 Date Published 12/1/2014 Volume : Pages 21 : 37 - 46 PubMed Reference 25419705 Abstract 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.

Investigators with authorship
Name Institution Erwin Bottinger Mount Sinai School of Medicine Ira Goldberg New York University School of Medicine Kumar Sharma University of California San Diego Katalin Susztak University of Pennsylvania

Complications
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