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Skeletal myosin heavy chain function in cultured lung myofibroblasts


Skeletal myosin heavy chain function in cultured lung myofibroblasts.

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Myofibroblasts are unique contractile cells with both muscle and nonmuscle properties. Typically myofibroblasts are identified by the expression of alpha smooth muscle actin (ASMA); however some myofibroblasts also express sarcomeric proteins. In this study, we show that pulmonary myofibroblasts express three of the eight known sarcomeric myosin heavy chains (MyHCs) (IIa, IId, and embryonic) and that skeletal muscle myosin enzymatic activity is required for pulmonary myofibroblast contractility. Furthermore, inhibition of skeletal myosin activity and myofibroblast contraction results in a decrease in both ASMA and skeletal MyHC promoter activity and ASMA protein expression, suggesting a potential coupling of skeletal myosin activity and ASMA expression in myofibroblast differentiation. To understand the molecular mechanisms whereby skeletal muscle genes are regulated in myofibroblasts, we have found that members of the myogenic regulatory factor family of transcription factors and Ca(2+) - regulated pathways are involved in skeletal MyHC promoter activity. Interestingly, the regulation of skeletal myosin expression in myofibroblasts is distinct from that observed in muscle cells and suggests that cell context is important in its control.


Rice NA, Leinwand LA

The Journal of cell biology

2003-10-13 00:00

163

1

119-29

Animals,Calcineurin,Cell Line,Lung,Myosin Heavy Chains,Promoter Regions (Genetics),Rats,Rats, Inbred Lew,Sarcomeres,Myosin Heavy Chains,Calcineurin

Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA

J. Cell Biol.

NHLBI F32-HL068485, NIGMS R01-GM29090

0021-9525

10.1083/jcb.200303194

jcb.200303194

785

True

14557251

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