RRC ID 10912
著者 Ikari A, Sanada A, Okude C, Sawada H, Yamazaki Y, Sugatani J, Miwa M.
タイトル Up-regulation of TRPM6 transcriptional activity by AP-1 in renal epithelial cells.
ジャーナル J Cell Physiol
Abstract Transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of magnesium in the kidney. We recently found that TRPM6 expression is up-regulated by EGF, but the regulatory mechanism has not been clear. TRPM6 mRNA was endogenously expressed in HEK293 cells. TRPM6 mRNA expression was increased by EGF, which was inhibited by U0126, an MEK inhibitor. Promoter activity of human TRPM6 was observed in the TRPM6 5'-flanking region from -1,214 to -718. This promoter activity was enhanced by EGF and inhibited by U0126. Three putative AP-1 binding sites were identified within the region of -1,214/-718. The mutation of the putative AP-1 binding site (-741/-736) completely inhibited the EGF-induced promoter activity. EGF increased p-ERK1/2, c-Fos, c-Jun, and p-c-Jun levels, which were inhibited by U0126. The introduction of c-Fos or c-Jun siRNA inhibited the EGF-induced promoter activity. A chromatin immunoprecipitation assay revealed that c-Fos and c-Jun bind to the AP-1 binding site within the region of -1,214/-718. These results suggest that EGF up-regulates TRPM6 mRNA expression mediate via the activation of ERK/AP-1-dependent pathway.
巻・号 222(3)
ページ 481-7
公開日 2010-3-1
DOI 10.1002/jcp.21988
PMID 19937979
MeSH 5' Flanking Region Animals Base Sequence Binding Sites Butadienes / pharmacology Cell Line Epidermal Growth Factor / metabolism* Epithelial Cells / drug effects Epithelial Cells / enzymology Epithelial Cells / metabolism* Humans Kidney / drug effects Kidney / enzymology Kidney / metabolism* MAP Kinase Kinase Kinases / antagonists & inhibitors MAP Kinase Kinase Kinases / metabolism Male Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Molecular Sequence Data Mutation Nitriles / pharmacology Phosphorylation Promoter Regions, Genetic Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-fos / metabolism Proto-Oncogene Proteins c-jun / metabolism RNA Interference RNA, Messenger / metabolism Rats Rats, Wistar TRPM Cation Channels / genetics TRPM Cation Channels / metabolism* Transcription Factor AP-1 / genetics Transcription Factor AP-1 / metabolism* Transcriptional Activation* / drug effects Transfection Up-Regulation
IF 5.546
引用数 22
WOS 分野 PHYSIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 293(RCB1637)