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

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 dep

SUBMITTER: Kang HM 

PROVIDER: S-EPMC4444078 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature