期刊
AMERICAN JOURNAL OF KIDNEY DISEASES
卷 43, 期 2, 页码 286-295出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.ajkd.2003.10.016
关键词
Gas6; angiotensin; kidney; signal transduction; NADPH oxidase
Background: Growth arrest-specific gene 6 (Gas6) and its binding partner, the receptor tyrosine kinase AxI, are important mediators in experimental nephritis. The authors tested whether the Gas6/Ax1 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 anti body-associated glomerulonephritis, acute transplant rejection, and normal renal tissue. Because reactive oxygen species are pivotal in inflammation, the authors tested whether the AxI/Gas6 expression is influenced by NADPH oxidase in vitro. Results: Gas6 and AxI immunofluorescence was barely detectable in normal kidney. However, in disease AxI 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 Ax1 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 X 10(-7) mol/L) for 6 or 18 hours. Confocal microscopy and Western blot showed Ang II-dependent Gas6 and AxI expression. An antisense probe against the p22 phox unit of NADPH-oxidase suppressed Ang II-induced Gas6 and AxI expression. In addition, in p47 phox knockout cells Ang II-induced Gas6 and Ax1 expression were blocked. Conclusion., GAS6/Ax1 signaling is involved in human renal disease. The Ang II-induced Gas6 and AxI expression may be dependent on NADPH-oxidase. Gas6 and AxI are important signaling molecules in human renal disease and may be potential therapeutic targets.
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