LOX-1 and inflammation: A new mechanism for renal injury in obesity and diabetes

Katherine Kelly, Pengfei Wu, Carolyn E. Patterson, Constance Temm, Jesus Dominguez

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The early nephropathy in obese, diabetic, dyslipidemic (ZS) rats is characterized by tubular lipid accumulation and pervasive inflammation, two critically interrelated events. We now tested the hypothesis that proximal tubules from ZS obese diabetic rats in vivo, and proximal tubule cells (NRK52E) exposed to oxidized LDL (oxLDL) in vitro, change their normally quiescent epithelial phenotype into a proinflammatory phenotype. Urine of obese diabetic rats contained more lipid peroxides, and LOX-1, a membrane receptor that internalizes oxidized lipids, was mobilized to luminal sites. Levels of ICAM-1 and focal adhesion kinase, which participate in leukocyte migration and epithelial dedifferentiation, respectively, were also upregulated in tubules. NRK52E cells exposed to oxLDL showed similar modifications, plus suppression of anti-inflammatory transcription factor peroxisome proliferator-activated receptor-δ. In addition, oxLDL impaired epithelial barrier function. These alterations were prevented by an anti-LOX-1 antibody. The data support the concept that tubular LOX-1 activation driven by lipid oxidants in the preurine fluid is critical in the inflammatory changes. We suggest that luminal lipid oxidants and abnormal tubular permeability may be partly responsible for the renal tubulointerstitial injury of obesity, diabetes, and dyslipidemia.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Obesity
Inflammation
Kidney
Lipids
Wounds and Injuries
Oxidants
Phenotype
Focal Adhesion Protein-Tyrosine Kinases
Peroxisome Proliferator-Activated Receptors
Lipid Peroxides
Intercellular Adhesion Molecule-1
Dyslipidemias
Permeability
Leukocytes
Anti-Inflammatory Agents
Transcription Factors
Urine
Membranes
Antibodies
oxidized low density lipoprotein

Keywords

  • Diabetic nephropathies
  • Epithelial permeability
  • Oxidized LDL receptors

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

LOX-1 and inflammation : A new mechanism for renal injury in obesity and diabetes. / Kelly, Katherine; Wu, Pengfei; Patterson, Carolyn E.; Temm, Constance; Dominguez, Jesus.

In: American Journal of Physiology - Renal Physiology, Vol. 294, No. 5, 05.2008.

Research output: Contribution to journalArticle

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