Linked Life Data

19667249

Source:http://linkedlifedata.com/resource/pubmed/id/19667249

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-9-17
pubmed:abstractText
Xanthine oxidoreductase (XOR) is an enzyme responsible for purine degradation, reactive oxygen species production, and adipogenesis. XOR gene-disrupted (XOR(-/-)) mice demonstrate renal failure and early death within several months. The aim of this study was to elucidate the mechanism of renal damage in XOR(-/-) mice and to determine the physiological role of XOR in the kidney. Histological analysis revealed that renal tubular damage in XOR(-/-) mice was accompanied by deposition of crystals and lipid-rich substances. Triglyceride content in renal homogenates was significantly increased in XOR(-/-) mice. The level of lipogenesis-related gene expression was comparable in XOR(+/+) and XOR(-/-) mice, whereas the expression of adipogenesis-related gene expression was significantly elevated in XOR(-/-) mice. Urinary excretions of xanthine and hypoxanthine were markedly elevated in XOR(-/-) mice. Immunohistochemical analysis, Western blotting, and real time RT-PCR revealed that various markers of fibrosis, inflammation, ischemia, and oxidative stress were increased in XOR(-/-) mice. Finally, we demonstrate that primary renal epithelial cells from XOR(-/-) mice are more readily transformed to myofibroblasts, which is a marker of increased epithelial mesenchymal transition. These results suggest that XOR gene disruption induced the depletion of uric acid and the accumulation of triglyceride-rich substances, xanthine, and hypoxanthine in the renal tubules. We believe that these changes contribute to a complex cellular milieu characterized by inflammation, tissue hypoxia, and reactive oxygen species production, ultimately resulting in renal failure through increased renal interstitial fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
868-76
pubmed:meshHeading
pubmed-meshheading:19667249-Adipogenesis, pubmed-meshheading:19667249-Animals, pubmed-meshheading:19667249-Disease Models, Animal, pubmed-meshheading:19667249-Epithelial Cells, pubmed-meshheading:19667249-Female, pubmed-meshheading:19667249-Fibrosis, pubmed-meshheading:19667249-Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), pubmed-meshheading:19667249-Hypoxanthine, pubmed-meshheading:19667249-Kidney Tubules, pubmed-meshheading:19667249-Lipid Metabolism, pubmed-meshheading:19667249-Lipogenesis, pubmed-meshheading:19667249-Male, pubmed-meshheading:19667249-Mice, pubmed-meshheading:19667249-Mice, Inbred C57BL, pubmed-meshheading:19667249-Mice, Knockout, pubmed-meshheading:19667249-Nephritis, Interstitial, pubmed-meshheading:19667249-Oxidative Stress, pubmed-meshheading:19667249-Purines, pubmed-meshheading:19667249-Triglycerides, pubmed-meshheading:19667249-Xanthine, pubmed-meshheading:19667249-Xanthine Dehydrogenase
pubmed:year
2009
pubmed:articleTitle
Xanthine oxidoreductase depletion induces renal interstitial fibrosis through aberrant lipid and purine accumulation in renal tubules.
pubmed:affiliation
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan. tohtsubo@intmed2.med.kyushu-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't