PMID- 11053056 OWN - NLM STAT- MEDLINE DCOM- 20001207 LR - 20211203 IS - 1931-857X (Print) IS - 1522-1466 (Linking) VI - 279 IP - 5 DP - 2000 Nov TI - Spontaneous shift in transcriptional profile of explanted glomeruli via activation of the MAP kinase family. PG - F954-9 AB - 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 NH(2)-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. FAU - Ishikawa, Y AU - Ishikawa Y AD - Renal Bioengineering Unit, Department of Medicine, University College Medical School, University College London, The Rayne Institute, London WC1E 6JJ, United Kingdom. FAU - Konta, T AU - Konta T FAU - Kitamura, M AU - Kitamura M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Chemokine CCL2) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 9005-49-6 (Heparin) RN - 9IKM0I5T1E (Quercetin) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, rat) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 1) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (Ptpro protein, rat) RN - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 3) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis/*genetics MH - Gene Expression/drug effects MH - Gene Expression Profiling MH - Heparin/pharmacology MH - JNK Mitogen-Activated Protein Kinases MH - Kidney Glomerulus/cytology/*metabolism MH - MAP Kinase Kinase 1 MH - Male MH - Matrix Metalloproteinase 3/biosynthesis/*genetics MH - Membrane Proteins/biosynthesis/genetics MH - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Nitric Oxide Synthase/biosynthesis/genetics MH - Nitric Oxide Synthase Type III MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/antagonists & inhibitors MH - Protein Tyrosine Phosphatases/biosynthesis/genetics MH - Proto-Oncogene Proteins c-fos/biosynthesis/genetics MH - Proto-Oncogene Proteins c-jun/biosynthesis/genetics MH - Quercetin/pharmacology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Receptor-Like Protein Tyrosine Phosphatases, Class 3 MH - Transcription Factor AP-1/antagonists & inhibitors/metabolism MH - Transcription, Genetic/physiology MH - p38 Mitogen-Activated Protein Kinases EDAT- 2000/10/29 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/29 11:00 PHST- 2000/10/29 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/29 11:00 [entrez] AID - 10.1152/ajprenal.2000.279.5.F954 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2000 Nov;279(5):F954-9. doi: 10.1152/ajprenal.2000.279.5.F954.