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Growth arrest specific protein 6/Axl signaling in human inflammatory renal diseases

Item Type:Article
Title:Growth arrest specific protein 6/Axl signaling in human inflammatory renal diseases
Creators Name:Fiebeler, A. and Park, J.K. and Muller, D.N. and Lindschau, C. and Mengel, M. and Merkel, S. and Banas, B. and Luft, F.C. and Haller, H.
Abstract:Background: Growth arrest-specific gene 6 (Gas6) and its binding partner, the receptor tyrosine kinase Axl, are important mediators in experimental nephritis. The authors tested whether the Gas6/Axl signaling pathway participates in human renal diseases. Methods: The authors compared 26 human renal specimens from patients with IgA nephritis, acute diffuse immune complex glomerulonephritis, acute lupus nephritis, antineutrophil cytoplasmic antibody-associated glomerulonephritis, acute transplant rejection, and normal renal tissue. Because reactive oxygen species are pivotal in inflammation, the authors tested whether the Axl/Gas6 expression is influenced by NADPH oxidase in vitro. Results: Gas6 and Axl immunofluorescence was barely detectable in normal kidney. However, in disease Axl was copiously expressed in the small vessel media, glomeruli, distal tubules, and collecting ducts. Similarly, Gas6 was upregulated in the small vessel intima and media, all segments of the renal tubules, the brush border, and glomeruli. Gas6 and Axl upregulation was a prominent but nonspecific finding in these renal diseases. Cultured rat vascular smooth muscle cells and immortalized human mesangial cells were stimulated with angiotensin (Ang) II (1 × 10-7 mol/L) for 6 or 18 hours. Confocal microscopy and Western blot showed Ang II-dependent Gas6 and Axl expression. An antisense probe against the p22 phox unit of NADPH-oxidase suppressed Ang II-induced Gas6 and Axl expression. In addition, in p47 phox knockout cells Ang II-induced Gas6 and Axl expression were blocked. Conclusion: GAS6/Axl signaling is involved in human renal disease. The Ang II-induced Gas6 and Axl expression may be dependent on NADPH-oxidase. Gas6 and Axl are important signaling molecules in human renal disease and may be potential therapeutic targets.
Keywords:Angiotensin, Gas6, Kidney, NADPH oxidase, Signal Transduction, Animals, Mice, Rats
Source:American Journal of Kidney Diseases
ISSN:0272-6386
Publisher:Saunders (U.S.A.)
Volume:43
Number:2
Page Range:286-295
Date:1 January 2004
Official Publication:https://doi.org/10.1053/j.ajkd.2003.10.016
PubMed:View item in PubMed

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