Published online before print February 10, 2005, doi: 10.1161/01.RES.0000158964.42008.a2
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Submitted on November 18, 2004
Revised on January 28, 2005
Accepted on January 31, 2005
Matrix Protein-Specific Regulation of Cx43 Expression in Cardiac Myocytes Subjected to Mechanical Load
Amit J. Shanker ;
From the Departments of Pathology and Medicine and the Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Mo.
* To whom correspondence should be addressed. E-mail: saffitz{at}pathology.wustl.edu.
To elucidate mechanisms responsible for mechanotransduction in the heart and define the effects of remodeling of the extracellular matrix, we cultured neonatal rat ventricular myocytes on native type I collagen, fibronectin, or denatured collagen and subjected them to uniaxial, pulsatile stretch. Changes in expression of the cardiac gap junction protein, Cx43, were measured by confocal microscopy and immunoblotting. Cells grown on fibronectin or denatured collagen exhibited significantly greater Cx43 expression than cells grown on native collagen. Stretch induced a 
2-fold increase in Cx43 expression in cells grown on native collagen but no increase in cells grown on fibronectin or denatured collagen. Incubation of cells on native collagen with a peptide containing the arginine-glycine-aspartate (RGD) motif upregulated Cx43 expression equivalent to that induced by stretch. Nonselective activation of integrin signaling with MnCl2 also upregulated Cx43 expression in cells grown on native collagen. This effect was blocked completely by pretreatment with anti-
1 integrin antibody but not by anti-3 integrin antibody. Stretch led to a marked increase in 1 integrin immunofluorescent signal in cells grown on native collagen but not in cells grown on fibronectin or denatured collagen. Stretch-induced upregulation of Cx43 was also blocked by anti-1 integrin antibody. Thus, matrix protein-myocyte interactions regulate Cx43 expression via 1 integrin signaling initiated by mechanical stimulation in cells grown on native type I collagen, or by RGD-integrin signaling independent of mechanical stress in cells grown on fibronectin or denatured collagen. Changes in the composition of the extracellular matrix may affect electrical coupling in cardiac myocytes.
Key words: cell culture • connexin43 expression • extracellular matrix • mechanical stretch • mechanotransduction
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