Title of article :
Activin A inhibits organization of sarcomeric proteins in cardiomyocytes induced by leukemia inhibitory factor
Author/Authors :
G. Florholmen، نويسنده , , B. Halvorsen، نويسنده , , K. Beraki، نويسنده , , T. Lyberg، نويسنده , , E.L. Sagen، نويسنده , , P. Aukrust، نويسنده , , G. Christensen، نويسنده , , A. Yndestad، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
Pages :
9
From page :
689
To page :
697
Abstract :
Cytokine systems are activated in heart failure, and it is believed that interaction between such systems may be important during progression of this disorder. We have previously shown that failing hearts have increased levels of the interleukin-6 related cytokine leukemia inhibitory factor (LIF) and activin A, a member of the transforming growth factor-β family. The aim of this study was to examine the effects of activin A on cardiomyocytes and a potential interaction with LIF-mediated changes in cell signaling and growth. Cardiomyocytes were isolated from 1- to 3-day-old Wistar rats, and the cells were treated with LIF, activin A or a combination thereof. Our main findings were: (i) activin A treatment reduced the LIF-mediated increase in cardiomyocyte length, perimeter and sarcomeric organization and was accompanied by a substantially decreased α-skeletal actin gene expression. (ii) The activin A-mediated phosphorylation of Smad2 was markedly enhanced by LIF. (iii) Activin A markedly induced SOCS3 gene expression, while LIF potently increased the expression of Smad7 mRNA, representing inhibitors of LIF and activin A signaling pathways, respectively. (iv) Inhibiting activation of the Smad2/3 pathway abolished the effects of activin A on LIF-induced changes in cell length, perimeter and sarcomeric organization. In conclusion, activin A markedly attenuates LIF-induced changes in cardiomyocytes, reflecting a potentially important role for both activin A and the Smad2/3 pathway in regulation of myocardial remodeling.
Keywords :
growth , Intracellular signaling , Isolated cardiomyocytes , Activin A , leukemia inhibitory factor
Journal title :
Journal of Molecular and Cellular Cardiology
Serial Year :
2006
Journal title :
Journal of Molecular and Cellular Cardiology
Record number :
529839
Link To Document :
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