133 67

Cited 0 times in

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

Authors
 Hyun Mi Kang  ;  Seon Ho Ahn  ;  Peter Choi  ;  Yi-An Ko  ;  Seung Hyeok Han  ;  Frank Chinga  ;  Ae Seo Deok Park  ;  Jianling Tao  ;  Kumar Sharma  ;  James Pullman  ;  Erwin P. Bottinger  ;  Ira J. Goldberg  ;  Katalin Susztak 
Citation
 Nature Medicine, Vol.21(1) : 37-46, 2015 
Journal Title
 Nature Medicine 
ISSN
 1078-8956 
Issue Date
2015
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140740
DOI
10.1038/nm.3762
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
한승혁(Han, Seung Hyeok)
사서에게 알리기
  feedback
Files in This Item:
T201502777.pdf Download
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse