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
Erwin BottingerMount Sinai School of Medicine
Ira GoldbergNew York University School of Medicine
Kumar SharmaUniversity of California San Diego
Katalin SusztakUniversity of Pennsylvania