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Erschienen in: Virchows Archiv 5/2005

01.11.2005 | Original Article

Transforming growth factor-β1 mediated up-regulation of lysyl oxidase in the kidneys of hereditary nephrotic mouse with chronic renal fibrosis

verfasst von: Yasufumi Goto, Kozue Uchio-Yamada, Sayuri Anan, Yoshie Yamamoto, Atsuo Ogura, Noboru Manabe

Erschienen in: Virchows Archiv | Ausgabe 5/2005

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Abstract

Lysyl oxidase (LOX), an extracellular emzyme, 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)-β1 (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-β1 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.
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Metadaten
Titel
Transforming growth factor-β1 mediated up-regulation of lysyl oxidase in the kidneys of hereditary nephrotic mouse with chronic renal fibrosis
verfasst von
Yasufumi Goto
Kozue Uchio-Yamada
Sayuri Anan
Yoshie Yamamoto
Atsuo Ogura
Noboru Manabe
Publikationsdatum
01.11.2005
Verlag
Springer-Verlag
Erschienen in
Virchows Archiv / Ausgabe 5/2005
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-005-0001-8

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