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The mRNAs encoding acidic FGF, basic FGF and FGF receptor are coordinately downregulated during myogenic
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Abstract:
Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that exert pleiotropic effects in a range of cell types including skeletal myocytes. Previous studies demonstrate that exogenously supplied FGFs stimulate proliferation of myoblasts and inhibit their differentiation in culture, but little information is available concerning endogenous expression of FGFs by skeletal myocytes. In this study acidic and basic FGF mRNAs were found to be expressed in murine and rat skeletal muscle, and expression was demonstrated to vary with the tissue and species examined. Myogenic cell lines were then analyzed to determine if FGFs are expressed in myoblasts, and if so, whether expression is regulated during myogenic differentiation. Murine Sol 8 and rat L6 myoblasts were found to express acidic and basic FGF mRNAs, and the expression of both growth factors was downregulated at the transcriptional level during myogenic differentiation. A decrease in expression of the mouse homologue of the human FGF receptor paralleled the decrease in acidic and basic FGF mRNAs in Sol 8 cells, indicating that the decrease in FGF receptor abundance previously observed during myogenic differentiation is regulated at the mRNA level. The results of this study suggest that a coordinate decrease in endogenously produced acidic and basic FGFs and their cognate receptor may participate in the regulation of myogenic differentiation. Furthermore, the observation that expression of a myogenic determination gene, myogenin, increases as FGF transcripts decline, together with previous data demonstrating suppression of myogenin expression by FGF, suggest a mechanism whereby endogenously produced FGFs may exert their effect on differentiation.
Insights
Endogenous acidic and basic fibroblast growth factors (FGFs) and their receptors are downregulated during skeletal muscle cell differentiation. This coordinated decrease may regulate myogenesis, as FGF transcripts decline while myogenin expression increases.
Area of Science:
- Cellular and Molecular Biology
- Muscle Physiology
- Developmental Biology
Background:
- Fibroblast growth factors (FGFs) influence various cell types, including skeletal myocytes.
- Exogenous FGFs promote myoblast proliferation and inhibit differentiation, but endogenous FGF expression in skeletal myocytes is poorly understood.
Purpose of the Study:
- To investigate the endogenous expression of acidic and basic FGFs and their receptor in skeletal myocytes.
- To determine if FGF expression is regulated during myogenic differentiation.
Main Methods:
- Analysis of acidic and basic FGF mRNA expression in murine and rat skeletal muscle.
- Examination of FGF mRNA and FGF receptor mRNA levels in myogenic cell lines (Sol 8 and L6) during differentiation.
- Quantitative assessment of gene expression changes.
Main Results:
- Acidic and basic FGF mRNAs are expressed in skeletal muscle, with variations across tissues and species.
- Both acidic and basic FGF mRNAs are downregulated at the transcriptional level during myogenic differentiation in Sol 8 and L6 cells.
- FGF receptor mRNA levels decrease in parallel with FGF mRNAs during differentiation in Sol 8 cells.
Conclusions:
- A coordinated downregulation of endogenous FGFs and their receptor may play a role in regulating myogenic differentiation.
- Declining FGF expression correlates with increasing myogenin expression, suggesting a mechanism for FGFs in differentiation control.