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Renal Bioengineering Unit, Department of Medicine, University College Medical School, University College London, The Rayne Institute, London WC1E 6JJ, United Kingdom
To understand how isolation and explantation of glomeruli affect the function of resident cells, the present study investigated the transcriptional profile of explanted normal glomeruli. We found that ex vivo incubation of glomeruli spontaneously expressed monocyte chemoattractant protein-1 (MCP-1) and stromelysin, the genes regulated by activator protein-1 (AP-1). The expression was suppressed by heparin and quercetin, the drugs with anti-AP-1 activities. The gene expression was preceded by 1) induction of AP-1 components c-fos and c-jun and 2) phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein (MAP) kinase, and c-Jun NH2-terminal kinase (JNK), the upstream inducers/activators of AP-1. Suppression of ERK by PD098059 abrogated induction of c-fos and c-jun, and the p38 MAP kinase inhibitor SB203580 attenuated c-fos expression. Furthermore, treatment with either PD098059, SB203580, or the JNK-AP-1 inhibitor curcumin diminished the expression of MCP-1 and stromelysin. The transcriptional profile of glomerular cells thus alters dramatically after explantation of glomeruli. It is, at least in part, due to activation of multiple MAP kinases that lead to induction of AP-1-dependent gene expression.
monocyte chemoattractant protein-1; stromelysin; extracellular signal-regulated kinase; p38 mitogen-activated protein kinase; c-Jun NH2 kinase
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K. Hayakawa, Y. Meng, N. Hiramatsu, A. Kasai, J. Yao, and M. Kitamura Spontaneous activation of the NF-{kappa}B signaling pathway in isolated normal glomeruli Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1169 - F1176. [Abstract] [Full Text] [PDF] |
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