Follistatin alters myostatin gene expression in C2C12 muscle cells

Kocamiş, Hakan; Gülmez, Nurhayat; Aslan, Şahin; Nazli, Mümtaz

doi:10.1556/avet.52.2004.2.1

Cited by 17 publications

(17 citation statements)

References 20 publications

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“…On the other hand, during the stage of complete regeneration, an absence of the myostatin and follistatin proteins and a marked decrease in the expression of both genes were observed 9 weeks after birth in both mouse strains. Interestingly, the myostatin mRNA level significantly increases in C2C12 cells treated with rh-follistatin at an early stage, but then sharply decreases at a late stage (Kocamis et al, 2004). This suggests that the beneficial effect of follistatin would occur in the presence of degenerative and necrotic muscle fibers.…”

Section: Discussionmentioning

confidence: 94%

Expression of Myostatin and Follistatin inMdxMice, an Animal Model for Muscular Dystrophy

et al. 2009

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Follistatin is a functional antagonist of several members of the TGF-β family of secreted signaling factors, including myostatin, the most powerful inhibitor of muscle growth characterized to date. Myostatin inhibition offers a novel therapeutic strategy for muscular dystrophy by restoring skeletal muscle mass and suppressing the progression of muscle degeneration. To assess the potential benefits of follistatin in treating muscle degenerative diseases, we examined the expression of myostatin and follistatin in Mdx mice, a model for Duchenne muscular dystrophy, and in B10 mice as a control. Our results demonstrated a temporary and coincident expression of follistatin and myostatin in both mouse strains, but this expression was significantly higher in Mdx mice than in B10 mice. The maximum expression of follistatin and myostatin in the presence of restoring necrotic muscle was detected 4 weeks after birth in Mdx mice. Interestingly, during the stage of complete regeneration, the absence of myostatin and follistatin proteins and a marked decrease in the expression of both genes were observed 9 weeks after birth in both mouse strains. These findings suggest that follistatin not only blocks myostatin but also allows other activators to function in muscle development, emphasizing that follistatin could be a very potent molecule in combating muscle loss during dystrophies and muscle ageing, disuse, or denervation.

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Section: Discussionmentioning

confidence: 94%

Expression of Myostatin and Follistatin inMdxMice, an Animal Model for Muscular Dystrophy

et al. 2009

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“…An antifibrotic process was simultaneously elicited, as evidenced by the stimulation of the expression of a) the myostatin activity inhibitor, follistatin (Hill et al 2002, Amthor et al 2004, Kocamis et al 2004, b) a Smad signaling inhibitor, Smad7 (Forbes et al 2006), and c) a collagen breakdown inducer, matrix metalloproteinase 8 (MMP-8;Siller-Lopez et al 2004). Follistatin did block the upregulation of TGF-b1 expression by myostatin, as shRNA against myostatin (Magee et al 2006) inhibited the expression of PAI-1, which in turn was stimulated autocrinely by the forced over-expression of myostatin.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to TGF-b1 and activin A, myostatin is inhibited by follistatin, and also by the agents that induce follistatin expression, such as deacetylase inhibitors that block myostatin negative action on the muscle (Lee & McPherron 2001, Amthor et al 2004, Iezzi et al 2004, Kocamis et al 2004. However, it is not known whether myostatin's putative profibrotic action is exerted via the stimulation of myofibroblasts differentiation from their progenitor, or by inducing a switch of the differentiated cell to the synthetic phenotype producing extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts

Artaza¹,

Singh²,

Ferrini³

et al. 2007

Journal of Endocrinology

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Tissue fibrosis, the excessive deposition of collagen/extracellular matrix combined with the reduction of the cell compartment, defines fibroproliferative diseases, a major cause of death and a public health burden. Key cellular processes in fibrosis include the generation of myofibroblasts from progenitor cells, and the activation or switch of already differentiated cells to a fibrotic synthetic phenotype. Myostatin, a negative regulator of skeletal muscle mass, is postulated to be involved in muscle fibrosis. We have examined whether myostatin affects the differentiation of a multipotent mesenchymal mouse cell line into myofibroblasts, and/or modulates the fibrotic phenotype and Smad expression of the cell population. In addition, we investigated the role of follistatin in this process. Incubation of cells with recombinant myostatin protein did not affect the proportion of myofibroblasts in the culture, but significantly upregulated the expression of fibrotic markers such as collagen and the key profibrotic factors transforming growth factor-b1 (TGF-b1) and plasminogen activator inhibitor (PAI-1), as well as Smad3 and 4, and the pSmad2/3. An antifibrotic process evidenced by the upregulation of follistatin, Smad7, and matrix metalloproteinase 8 accompanied these changes. Follistatin inhibited TGF-b1 induction by myostatin. Transfection with a cDNA expressing myostatin upregulated PAI-1, whereas an shRNA against myostatin blocked this effect. In conclusion, myostatin induced a fibrotic phenotype without significantly affecting differentiation into myofibroblasts. The concurrent endogenous antifibrotic reaction confirms the view that phenotypic switches in multipotent and differentiated cells may affect the progress or reversion of fibrosis, and that myostatin pharmacological inactivation may be a novel therapeutic target against fibrosis.

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“…Based these findings, we carried out in vivo follistatin administration during the neonatal period in an attempt to neutralize myostatin activity. Kocamis et al [45] showed that myostatin gene expression in C2C12 cells was acutely increased by the addition of recombinant human follistatin, indicating the possibility that follistatin modulates myostatin gene expression in skeletal muscle. However, the results obtained in the present experiment revealed that both myostatin gene expression in skeletal muscle and the protein level in serum were not altered by follistatin when adm i nistra t e d i n v iv o, in d ic at i n g t h a t th e hypertrophic effect of follistatin on skeletal muscle fiber was not due to alteration of myostatin expression.…”

Section: Discussionmentioning

confidence: 99%

Role of Serum Myostatin during the Lactation Period

Hosoyama

Yamanouchi

Nishihara

2006

Journal of Reproduction and Development

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Abstract. Myostatin, also known as GDF-8 (Growth/Differentiation Factor-8), is a member of the TGF-β superfamily that negatively regulates skeletal muscle mass in mammals. Mutation of the myostatin gene in mice, cattle, and humans causes a massively developed skeletal muscle, characterized by muscle hypertrophy and hyperplasia. Although myostatin is predominantly expressed in skeletal muscle tissue, several recent studies have shown the presence of myostatin protein in blood and suggested a possible role for circulating myostatin in the regulation of skeletal muscle mass. In the present study, we examined changes in the levels of active form myostatin (13 kDa) in serum after birth by Western blot analysis to predict the role of serum myostatin in early postnatal muscle growth in the rat. Interestingly, the amount of active form myostatin in serum increased after birth and then decreased along with ageing after weaning. To clarify the role of increased serum myostatin during the postnatal period, we administrated follistatin, an inhibitor of myostatin activity, into postnatal rats intraperitoneally just after birth. Follistatin-administration during the postnatal period caused selective hypertrophy of type II muscle fibers in the soleus muscle. These results demonstrate that myostatin in serum acts on skeletal muscle and negatively regulates early postnatal muscle growth.

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Follistatin alters myostatin gene expression in C2C12 muscle cells

Cited by 17 publications

References 20 publications

Expression of Myostatin and Follistatin inMdxMice, an Animal Model for Muscular Dystrophy

Expression of Myostatin and Follistatin inMdxMice, an Animal Model for Muscular Dystrophy

Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts

Role of Serum Myostatin during the Lactation Period

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