| Autor: |
K, Takazoe, R, Foti, La, Hurst, Rc, Atkins, DJ., Nikolic-Paterson |
| Předmět: |
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| Zdroj: |
Nephrology; Oct2000, Vol. 5 Issue 3, pA92, 1p |
| Abstrakt: |
CD44 is a cell-surface adhesion molecule expressed by leukocytes and some tubular epithelium and is up-regulated in glomerulonephritis (GN). CD44 may play a role in disease pathogenesis on the basis that blocking one of its ligands, osteopontin, causes significant inhibition of rat crescentic anti-GBM GN. We have previously shown that IL-1 up-regulates tubular CD44 expression on the basis that IL-1 receptor antagonist treatment reduces tubular CD44 expression in rat anti-GBM GN. There is a binding site for the transcription factor Egr-1 in the CD44 gene promoter, therefore we examined the role of Egr-1 in IL-1 induced tubular CD44 expression in vitro. The NRK52E tubular epithelial cell line constitutively expresses low levels of CD44 mRNA and protein, with barely detectable levels of Egr-1 mRNA or protein. Northern blotting showed that the addition of IL-1 to NRK52E cells induced a transient peak of Egr-1 mRNA expression at 30 minutes, which was followed by a 3-fold increase in CD44 mRNA at 6 hours and an increase in CD44 protein expression on the cell surface at 18 hours. In contrast, the rat macrophage line NR8383 constitutively expresses high levels of both Egr-1 and CD44, and IL-1 stimulation had no effect upon CD44 mRNA or protein expression in these cells. In preliminary studies, Egr-1 anti-sense oligonucleotides (10μM) caused a 42-49% reduction in IL-1 induced CD44 protein expression in NRK52E cells using a cell-based ELISA. In conclusion, these data argue that IL-1 up-regulates tubular CD44 expression via the transcription factor Egr-1. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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