u-0126 and Kidney-Failure--Chronic

u-0126 has been researched along with Kidney-Failure--Chronic* in 1 studies

Other Studies

1 other study(ies) available for u-0126 and Kidney-Failure--Chronic

ArticleYear
Renal upregulation of HO-1 reduces albumin-driven MCP-1 production: implications for chronic kidney disease.
    American journal of physiology. Renal physiology, 2007, Volume: 292, Issue:2

    Proteinuria contributes to chronic kidney disease by stimulating renal tubular epithelial cells to produce cytokines such as monocyte chemoattractant protein-1 (MCP-1). The present study determined whether cellular overexpression of heme oxygenase-1 (HO-1) can influence albumin-stimulated MCP-1 production. In response to bovine serum albumin, NRK-52E cells constitutively overexpressing HO-1 (HO-1 OE cells) exhibit less induction of MCP-1 mRNA and less production of MCP-1 protein compared with similarly treated, control NRK-52E cells (CON cells). In wild-type NRK-52E cells, and under these conditions, we demonstrate that the induction of MCP-1 is critically dependent on intact NF-kappaB binding sites in the MCP-1 promoter. In response to albumin, CON cells exhibit activation of NF-kappaB, and this is reduced in HO-1 OE cells. Albumin also activates ERK1/2 and increases ERK activity, both of which are exaggerated in HO-1 OE cells. Studies with an inhibitor of MAPK/ERK kinase (U0126) demonstrate that the inhibitory effects of U0126 on MCP-1 production are attenuated in HO-1 OE cells. We conclude that HO-1 overexpression in the proximal tubule reduces MCP-1 production in response to albumin, and this occurs, at least in part, by inhibiting an ERK-dependent, NF-kappaB-dependent pathway at a site that is distal to the activation of ERK. These findings suggest that the induction of HO-1 in the proximal tubule, as occurs in chronic kidney disease, may be a countervailing response that reduces albumin-stimulated production of cytokines such as MCP-1.

    Topics: Animals; Butadienes; Cell Line; Chemokine CCL2; Extracellular Signal-Regulated MAP Kinases; Heme Oxygenase-1; Kidney; Kidney Failure, Chronic; Kidney Tubules, Proximal; NF-kappa B; Nitriles; Rats; Serum Albumin, Bovine; Up-Regulation

2007