Mechanisms of endothelin-1 mRNA and peptides induction by TGF-β and TPA in MDCK cells

M. Horie, S. Uchida, M. Yanagisawa, Y. Matsushita, K. Kurokawa, E. Ogata

Research output: Contribution to journalArticle

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Abstract

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 (~2.3 kb). TGF-β time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-β 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 μg/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-β treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 μM 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-β. An axis of TGF-β-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume17
Issue numberSUPPL. 7
StatePublished - 1991

Fingerprint

Madin Darby Canine Kidney Cells
Endothelin-1
Messenger RNA
Peptides
Dactinomycin
Phorbol Esters
Electrolytes
Half-Life
Down-Regulation
Dogs
Kidney
Growth

Keywords

  • Actinomycin D
  • Endothelin-1
  • MDCK cells
  • Preproendothelin-1 mRNA
  • TGF-β
  • TPA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Mechanisms of endothelin-1 mRNA and peptides induction by TGF-β and TPA in MDCK cells. / Horie, M.; Uchida, S.; Yanagisawa, M.; Matsushita, Y.; Kurokawa, K.; Ogata, E.

In: Journal of Cardiovascular Pharmacology, Vol. 17, No. SUPPL. 7, 1991.

Research output: Contribution to journalArticle

Horie, M, Uchida, S, Yanagisawa, M, Matsushita, Y, Kurokawa, K & Ogata, E 1991, 'Mechanisms of endothelin-1 mRNA and peptides induction by TGF-β and TPA in MDCK cells', Journal of Cardiovascular Pharmacology, vol. 17, no. SUPPL. 7.
Horie, M. ; Uchida, S. ; Yanagisawa, M. ; Matsushita, Y. ; Kurokawa, K. ; Ogata, E. / Mechanisms of endothelin-1 mRNA and peptides induction by TGF-β and TPA in MDCK cells. In: Journal of Cardiovascular Pharmacology. 1991 ; Vol. 17, No. SUPPL. 7.
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AU - Horie, M.

AU - Uchida, S.

AU - Yanagisawa, M.

AU - Matsushita, Y.

AU - Kurokawa, K.

AU - Ogata, E.

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N2 - 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 (~2.3 kb). TGF-β time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-β 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 μg/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-β treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 μM 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-β. An axis of TGF-β-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.

AB - 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 (~2.3 kb). TGF-β time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-β 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 μg/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-β treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 μM 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-β. An axis of TGF-β-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.

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