A novel p38 MAPK target dyxin is rapidly induced by mechanical load in the heart

Hanne Luosujrvi, Jani Aro, Heikki Tokola, Hanna Leskinen, Olli Tenhunen, Réka Skoumal, Istvn Szokodi, Heikki Ruskoaho, Jaana Rys

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Dyxin is a novel LIM domain protein acting as a transcriptional cofactor with GATA transcription factors. Here, we characterized dyxin as a p38 mitogen-activated protein kinase (MAPK) regulated gene, since combined upstream MAPK kinase 3b and wild-type p38α MAPK gene transfer increased left ventricular dyxin mRNA and protein levels in vivo. We also studied cardiac dyxin expression in experimental models of pressure overload and myocardial infarction (MI) in vivo. Angiotensin II infusion increased left ventricular dyxin mRNA levels (9.4-fold, p<0.001) rapidly at 6 h followed by induction of protein levels. Furthermore, simultaneous administration of p38 MAPK inhibitor SB203580 abolished angiotensin II-induced activation of dyxin gene expression. During the post-infarction remodeling process, increased dyxin mRNA levels (7.7-fold, p<0.01) were noted at day 1 followed by the increase in proteins levels at 2 weeks after MI (1.5-fold, p<0.05). Moreover, direct wall stretch by using isolated rat heart preparation as well as direct mechanical stretch of cardiomyocytes in vitro activated dyxin gene expression within 1 h. Our results indicate that dyxin expression is rapidly upregulated in response to mechanical load, this increase being at least partly mediated by p38 MAPK. These results suggest that dyxin may play an important role in regulating hypertrophic process.

Original languageEnglish
Pages (from-to)54-63
Number of pages10
JournalBlood pressure
Volume19
Issue number1
DOIs
Publication statusPublished - Mar 8 2010

    Fingerprint

Keywords

  • Cardiac hypertrophy
  • Lmcd1
  • Myocardial infarction
  • P38 MAPK
  • Pressure overload
  • Remodeling

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Luosujrvi, H., Aro, J., Tokola, H., Leskinen, H., Tenhunen, O., Skoumal, R., Szokodi, I., Ruskoaho, H., & Rys, J. (2010). A novel p38 MAPK target dyxin is rapidly induced by mechanical load in the heart. Blood pressure, 19(1), 54-63. https://doi.org/10.3109/08037050903464519