Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-11-30
pubmed:abstractText
Lysyl oxidase (LOX), an extracellular enzyme, plays a key role in the post-translational modification of collagens and elastin, catalyzing inter- and intra-crosslinking reactions. Because the crosslinked extracellular matrices (ECMs) are highly resistant to degradative enzymes, it is considered that the over-expression of LOX may cause severe fibrotic degeneration. In the present study, we addressed the role of LOX-mediated crosslinking in chronic renal tubulointerstitial fibrosis using an animal model of hereditary nephrotic syndrome, the Institute of Cancer Research (ICR)-derived glomerulonephritis (ICGN) mouse. Ribonuclease protection assay (RPA) revealed that LOX mRNA expression was up-regulated in the kidneys of ICGN mice as compared with control ICR mice. High-level expression of LOX and transforming growth factor (TGF)-beta1 (an up-regulator of LOX) mRNA was detected in tubular epithelial cells of ICGN mouse kidneys by in situ hybridization. Type-I and -III collagens, major substrates for LOX, were accumulated in tubulointerstitium of ICGN mouse kidneys. The present findings imply that TGF-beta1 up-regulates the production of LOX in tubular epithelial cells of ICGN mouse kidneys, and the excessive LOX acts on interstitial collagens and catalyzes crosslinking reactions. As a result, the highly crosslinked collagens induce an irreversible progression of chronic renal tubulointerstitial fibrosis in the kidneys of ICGN mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0945-6317
pubmed:author
pubmed:issnType
Print
pubmed:volume
447
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
859-68
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16086153-Animals, pubmed-meshheading:16086153-Cells, Cultured, pubmed-meshheading:16086153-Chronic Disease, pubmed-meshheading:16086153-Disease Models, Animal, pubmed-meshheading:16086153-Dose-Response Relationship, Drug, pubmed-meshheading:16086153-Epithelial Cells, pubmed-meshheading:16086153-Female, pubmed-meshheading:16086153-Fibrosis, pubmed-meshheading:16086153-Glomerulonephritis, pubmed-meshheading:16086153-Humans, pubmed-meshheading:16086153-In Situ Hybridization, pubmed-meshheading:16086153-Kidney, pubmed-meshheading:16086153-Kidney Tubules, pubmed-meshheading:16086153-Male, pubmed-meshheading:16086153-Mice, pubmed-meshheading:16086153-Mice, Inbred ICR, pubmed-meshheading:16086153-Nephrotic Syndrome, pubmed-meshheading:16086153-Protein-Lysine 6-Oxidase, pubmed-meshheading:16086153-RNA, Messenger, pubmed-meshheading:16086153-Transforming Growth Factor beta, pubmed-meshheading:16086153-Transforming Growth Factor beta1, pubmed-meshheading:16086153-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Transforming growth factor-beta1 mediated up-regulation of lysyl oxidase in the kidneys of hereditary nephrotic mouse with chronic renal fibrosis.
pubmed:affiliation
Research Unit for Animal Life Sciences, Animal Resource Science Center, The University of Tokyo, 3145 Ago, Ibaraki-Iwama, 319-0206, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't