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Opposing effects of activin A and follistatin on developing skeletal muscle cells. Exp Cell Res 1997 Jun 15;233(2):350-62

Date

06/15/1997

Pubmed ID

9194497

DOI

10.1006/excr.1997.3575

Scopus ID

2-s2.0-0031570780   49 Citations

Abstract

Activin and the activin-binding protein follistatin modulate a variety of biological processes and are abundant at sites of muscle development. Activin and follistatin were expressed in developing chick pectoral muscle in vivo and in primary cell culture. Addition of recombinant activin inhibited muscle development in a dose-dependent manner as measured by the number of nuclei in myosin heavy chain positive cells and creatine phosphokinase activity. Conversely, follistatin potentiated muscle development. The effects of activin were found to be distinct from those of the related protein transforming growth factor (TGF) beta1. Muscle development was repressed by activin at all time points investigated and did not recover with the removal of activin following a limited exposure. In contrast, while myogenic differentiation in TGFbeta1 was initially repressed, muscle marker expression recovered to control levels--even in the continued presence of TGFbeta1. Fibroblast growth factor (FGF) had little effect on inhibiton of muscle development caused by activin A. However, inhibition of development produced by TGFbeta increased with increasing concentrations of FGF. Finally, early expression of myoD and myf5 mRNA by muscle cultures in the presence of activin and follistatin was analyzed. Activin-treated cultures expressed reduced myoD and myf5 levels at 1.5 days after plating. Myf5 levels in follistatin-treated cultures were elevated, but, surprisingly, these cultures showed a reduction in myoD levels. These data suggest that endogenously expressed activin and follistatin are important modulators of muscle development.

Author List

Link BA, Nishi R

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Activins
Animals
Cell Nucleus
Cells, Cultured
Chick Embryo
Creatine Kinase
DNA-Binding Proteins
Fibroblast Growth Factors
Fluorescent Antibody Technique, Indirect
Follistatin
Gene Expression
Glycoproteins
Inhibins
Muscle Proteins
Muscle, Skeletal
MyoD Protein
Myogenic Regulatory Factor 5
RNA, Messenger
Trans-Activators
Transforming Growth Factor beta
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0