TWIST1 regulates the activity of ubiquitin proteasome system via the miR-199/214 cluster in human end-stage dilated cardiomyopathy

Anna Baumgarten, Claudia Bang, Anika Tschirner, Anke Engelmann, Volker Adams, Stephan Von Haehling, Wolfram Doehner, Reinhard Pregla, Markus S. Anker, Kinga Blecharz, Rudolf Meyer, Roland Hetzer, Stefan D. Anker, Thomas Thum, Jochen Springer

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The transcription factor TWIST1 has been described to regulate the microRNA (miR)-199/214 cluster. Genetic disruption of TWIST1 resulted in a cachectic phenotype and early death of the knock-out mice. This might be connected to the activity of the ubiquitin-proteasome-system (UPS), as miR-199a has been suggested to regulate the ubiquitin E2 ligases Ube2i and Ube2g1. Methods: Cardiac tissue from explanted hearts of 42 patients with dilated cardiomyopathy and 20 healthy donor hearts were analysed for protein expression of TWIST1 and its inhibitors Id-1, MuRF-1 and MAFbx, the expression of miR-199a, -199b and -214, as well as the activity of the UPS by using specific fluorogenic substrates. Results: TWIST1 was repressed in patients with dilated cardiomyopathy by 43% (p=0.003), while Id1 expression was unchanged. This was paralleled by a reduced expression of miR-199a by 38±9% (p=0.053), miR-199b by 36±13% (p=0.019) and miR-214 by 41±11% (p=0.0158) compared to donor hearts. An increased peptidylglutamyl-peptide-hydrolysing activity (p

Original languageEnglish
Pages (from-to)1447-1452
Number of pages6
JournalInternational Journal of Cardiology
Volume168
Issue number2
DOIs
Publication statusPublished - Sep 30 2013

Keywords

  • Cardiomyopathy
  • DCM
  • MicroRNA
  • TWIST1
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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