Decreased extracellular chloride increased COX-2 expression by 3.9-fold in cultured cTALH cells, an effect mediated by activation of a p38-dependent signaling pathway.
Does reduced extracellular chloride increase COX-2 expression via a p38-dependent pathway in cTALH cells and rat renal cortex?
Reduced extracellular chloride increases COX-2 expression in the macula densa and cTALH via a p38-dependent signaling pathway, providing a mechanism for macula densa regulation of renin expression.
Absolute Event Rate: 3.9% vs 1%
p-value: p=<0.01
We have previously shown that in renal cortex, COX-2 expression is localized to macula densa and surrounding cortical thick ascending limb of Henle (cTALH). Dietary salt restriction increases local expression of COX-2, which mediates renin production and secretion. Given that decreased luminal chloride Cl(-) at the level of the macula densa increases renin production and secretion, we investigated the role of extracellular ion concentration on COX-2 expression. Quiescent rabbit cTALH cells were incubated in a physiological salt solution containing high or low levels of NaCl. Immunoreactive COX-2 expression increased significantly in the low NaCl solution. COX-2 expression also increased after administration of the Na(+)/K(+)/2Cl(-) cotransport inhibitor, bumetanide. Selective substitution of chloride led to increased COX-2 expression, whereas selective substitution of sodium had no effect. The p38 MAP kinase inhibitor PD169316 decreased low NaCl-induced COX-2 expression. Low-salt or low-chloride medium induced cultured cTALH to accumulate >/= 3-fold higher levels of pp38, the activated (phosphorylated) form of p38; low-salt medium also increased pJNK and pERK levels. Feeding rats a low-salt diet for 14 days induced a significant increase in renal cortical pp38 expression, predominantly in the macula densa and cTALH. These results suggest that reduced extracellular chloride leads to increased COX-2 expression, which may be mediated by activation of a p38-dependent signaling pathway.
Cheng et al. (Fri,) conducted a other in Renal cortical cyclooxygenase-2 expression regulation. Low extracellular chloride / Low salt diet vs. Normal salt diet / Normal salt medium was evaluated on Immunoreactive COX-2 expression (fold control) (p=<0.01). Decreased extracellular chloride increased COX-2 expression by 3.9-fold in cultured cTALH cells, an effect mediated by activation of a p38-dependent signaling pathway.