Journal article

Publication year: 2010

Pages: 621-629

Journal: Basic Research in Cardiology

Volume number: 105

Issue number: 5

ISSN: 0300-8428

eISSN: 1435-1803

DOI Link: https://doi.org/10.1007/s00395-010-0108-1

Publisher: Springer

Abstract: 
TGF-beta 1 plays an important role in cardiac fibrosis, apoptosis, induction of hypertrophy and contractile dysfunction. This study investigates whether TGF-beta 1 plays a role in laminin receptor 37/67 (37/67 LR)-dependent regulation of cardiac performance. Therefore, isolated adult cardiomyocytes were stimulated with TGF-beta 1, the expression of the 37/67 LR was determined and cell shortening was investigated on cells attached to a non-specific, serum-based attachment substrate or to specific, laminin-coated dishes. The role of the MAP kinases in TGF-beta 1-dependent induction of the 37/67 LR was examined by addition of PD98059, SB202190 and SP600125. Finally, the expression of receptor mRNA was investigated in transgenic mice constitutively over-expressing TGF-beta 1 and the relationship to distress score and lung wet weight-to-body weight was analysed. TGF-beta 1 induced a significant increase of the 37/67 LR mRNA and protein expression. The cytokine induced p38 MAP kinase and JNK, but not ERK. Inhibition of either p38 MAP kinase or JNK attenuated the TGF-beta 1-dependent increase in 37/67 LR expression. TGF-beta 1 induced a loss of cell shortening in cells attached to a non-specific substrate, but not in cells on a pre-coated laminin matrix. Inhibition of JNK attenuated the protective effect of laminin receptor up-regulation on cardiac performance. Inhibition of p38 MAP kinase attenuated the depressive effect of TGF-beta 1 on basal cell shortening. In transgenic mice over-expressing TGF-beta 1 a strong induction of laminin receptor expression attenuated the severeness of the mice' symptoms. This study shows a new and protective role of TGF-beta 1-dependent up-regulation of the 37/67 LR in cardiomyocytes in cardiac remodelling with increased laminin expression.

Harvard Citation style: Wenzel, S., Henning, K., Habbig, A., Forst, S., Schreckenberg, R., Heger, J., et al. (2010) TGF-β1 improves cardiac performance via up-regulation of laminin receptor 37/67 in adult ventricular cardiomyocytes, Basic Research in Cardiology, 105(5), pp. 621-629. https://doi.org/10.1007/s00395-010-0108-1

APA Citation style: Wenzel, S., Henning, K., Habbig, A., Forst, S., Schreckenberg, R., Heger, J., Maxeiner, H., & Schlueter, K. (2010). TGF-β1 improves cardiac performance via up-regulation of laminin receptor 37/67 in adult ventricular cardiomyocytes. Basic Research in Cardiology. 105(5), 621-629. https://doi.org/10.1007/s00395-010-0108-1