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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark
TGF-BETA1 IMPROVES CARDIAC PERFORMANCE VIA UP-REGULATION OF LAMININ-RECEPTOR 37/67 IN ADULT VENTRICULAR CARDIOMYOCYTES
Abstract number: P-MON-15
Wenzel1 S, Henning1 K, Habbig1 A, Forst1 S, Schreckenberg1 R, Heger1 J, Maxeiner1 H, Schluter1 K-D
TGF-beta1 plays an important role in various processes of cardiac remodelling. This study investigates whether TGF-beta engages a role in laminin-receptor 37/67-dependent regulation of cardiac performance. Cardiomyocytes were stimulated with TGF-beta and the expression of the non-integrin-laminin-receptor 37/67 was determined by immunoblotting and real-time RT-PCR. The phosphorylation of mitogen-activated kinases in response to TGF-beta was analysed and their role in TGF-beta-dependent induction of laminin-receptor 37/67 was investigated by addition of PD98059, SB202190, and SP600125. Cell shortening of cardiomyocytes was investigated on cells attached to a non-specific serum-based attachment substrate or specific laminin-coated dishes. Finally, the expression of the receptor mRNA was investigated in transgenic mice constitutively over-expressing TGF-beta and the relationship to distress scoring an lung wet weight-to-body weight as determinants of heart failure was analysed. TGF-beta induced a significant increase of cardiac-specific laminin-receptor 37/67 mRNA and protein expression. The cytokine induced p38 MAPK and JNK, but nor ERK. Inhibition of either p38 MAPK or JNK attenuated the effect of TGF-beta-induced receptor expression. TGF-beta induced a loss of cell shortening in cell attached to a non-specific substrate but not in cells pre-coated on a laminin matrix. Inhibition of JNK attenuated the protective effect of laminin-receptor up-regulation on cardiac performance. Inhibition of p38 MAPK attenuated the depressive effect of TGF-beta on basal cell shortening. In transgenic mice over-expressing TGF-beta a strong induction of laminin-receptor expression attenuated the illness of the mice. This study shows a new and protective role of TGF-beta-dependent up-regulation of laminin-receptor 37/67 in cardiomyocytes with fibroblast-dependent laminin expression.
To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 198, Supplement 677 :P-MON-15