Mechanisms of endothelin-1 mRNA and peptides induction by TGF-beta and TPA in MDCK cells.
Mechanisms of prepro-ET-1 mRNA expression and mature endothelin-1 (ET-1) peptide secretion in MDCK cells (dog collecting duct origin) were investigated. MDCK cells constitutively expressed prepro-ET-1 mRNA (approximately 2.3 kb). TGF-beta time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-beta addition was dose-dependent with a half-maximal concentration of 10 pM. The half-life of prepro-ET-1 mRNA was 15 min in controls when the cells were treated with 10 micrograms/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-beta treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 microM TPA, one of the phorbol esters, but downregulated below baseline after 1 h. Our data show that MDCK cells constitutively secrete ET-1 and increase its production in response to TGF-beta. An axis of TGF-beta-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.
Horie
M
M
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Uchida
S
S
Yanagisawa
M
M
Matsushita
Y
Y
Kurokawa
K
K
Ogata
E
E
D000818:Animals; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004285:Dogs; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D013755:Tetradecanoylphorbol Acetate