Myostatin gene promoter: structure, conservation and importance as a target for muscle modulation

Grade, Carla Vermeulen Carvalho; Mantovani, Carolina Stefano; Alvares, Lúcia Elvira

doi:10.1186/s40104-019-0338-5

Cited by 37 publications

(37 citation statements)

References 115 publications

(200 reference statements)

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“…MSTN is a member of the TGFβ family and acts as a phylogenetically conserved negative regulator of muscle mass [ 31 ]. The MSTN protein is synthesized mostly in muscle, adipose, and cardiac tissues, where it secreted and present as an extracellular matrix-resident [ 32 ]. The clinical relevance of myostatin is predominantly in treating muscle wasting diseases, obesity and type 2 diabetes [ 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

The extracellular matrix phenome across species

Statzer

Ewald

2020

Matrix Biology Plus

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Extracellular matrices are essential for cellular and organismal function. Recent genome-wide and phenome-wide association studies started to reveal a broad spectrum of phenotypes associated with genetic variants. However, the phenome or spectrum of all phenotypes associated with genetic variants in extracellular matrix genes is unknown. Here, we analyzed over two million recorded genotype-to-phenotype relationships across multiple species to define their extracellular matrix phenomes. By using the previously defined matrisomes of humans, mice, zebrafish, Drosophila, and C. elegans , we found that the extracellular matrix phenome comprises of 3–10% of the entire phenome. Collagens ( COL1A1 , COL2A1 ) and fibrillin ( FBN1 ) are each associated with >150 distinct phenotypes in humans, whereas collagen COL4A1 , Wnt- and sonic hedgehog (shh) signaling are predominantly associated in other species. We determined the phenotypic fingerprints of matrisome genes and found that MSTN, CTSD, LAMB2, HSPG2 , and COL11A2 and their corresponding orthologues have the most phenotypes across species. Out of the 42,551 unique matrisome genotype-to-phenotype relationships across the five species with defined matrisomes, we have constructed interaction networks to identify the underlying molecular components connecting with orthologues phenotypes and with novel phenotypes. Thus, our networks provide a framework to predict unassessed phenotypes and their potential underlying molecular interactions. These frameworks inform on matrisome genotype-to-phenotype relationships and potentially provide a sophisticated choice of biological model system to study human phenotypes and diseases.

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Section: Resultsmentioning

confidence: 99%

The extracellular matrix phenome across species

Statzer

Ewald

2020

Matrix Biology Plus

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“…The leucine effects on myostatin mRNA during immobilization could be related to transcription and posttranscriptional modulation. At transcriptional level, myostatin expression can be induced by the transcription factor FoxO (Allen and Unterman, 2007;Grade et al, 2019). Accordingly, FoxO activity is increased in disuse atrophy (Senf et al, 2010;Baptista et al, 2017) and leucine supplementation is able to decrease FoxO nuclear translocation during immobilization (Baptista et al, 2017).…”

mentioning

confidence: 99%

“…For example, follistatin mRNA could generate a currently uncharacterized microRNAs that would, in turn, be able to inhibit mRNAs coding for stimulators of myostatin, such as NF-kb-p65, MYOD, MYF5, and NFAT, all of which are known to be transactivators of the myostatin promoter. Alternatively, those microRNAs could even target myostatin mRNA itself (Huang et al, 2012;Qiu et al, 2013;Grade et al, 2019).…”

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confidence: 99%

Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition

Cruz

Ferian

Alves

et al. 2020

DNA and Cell Biology

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Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by realtime PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling.

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“…Peningkatan otot ini merupakan hasil dari pengaruh MSTN terhadap gen-gen pengontrol siklus sel yang menyebabkan sel-sel progenitor myogenik secara permanen menarik diri dari siklus sel (Joulia et al 2003). Selain itu, MSTN merupakan penghambat proliferasi progenitor sel-sel otot rangka selama masa perkembangan hewan hingga saat terbentuknya ukuran otot rangka setelah lahir (Grade et al 2019).…”

Section: Gambar 1 Struktur Protein Myostatin Dan Mutasi Alamiunclassified

Myostatin Gene as a Genetic Marker for Growth and Carcass Traits in Beef Cattle

Prihandini¹,

Hariyono

Tribudi

2021

WARTAZOA

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<p>Growth and carcass traits are of economic importances in livestock breeding, because they affect the profitability of animal production. The phenotypic expression of these traits is controlled by multiple genes (polygenes), such as myostatin (MSTN) gene. This paper aims to discuss the expression, polymorphism and potential application of MSTN gene as a marker-assisted selection (MAS) for growth and carcass traits in beef cattle based on data from published studies. MSTN gene or known as growth and differentiation factor 8 (GDF8) is a member of the transforming growth factor-β (TGF-β) superfamily, which acts as a negative regulator of skeletal muscle mass deposition. Several published studies showed that mutations in the MSTN gene can inhibit the activation of myostatin, which leads to an increased muscle mass (hypertrophy). Several <em>MSTN</em> gene polymorphisms were reported to be associated with growth and carcass traits in local cattle in several countries, including Indonesia, namely Bali cattle. Based on several assumptions: 1) there is MTSN gene polymorphisms in a population, 2) there is a significant association between MSTN gene polymorphisms and growth and carcass traits, as reported in several beef cattle populations and 3) those cattle with superior genotype have better growth performances, we expect that there will be improvement in growth performances in the future if those cattle are selected. Understanding MSTN gene polymorphisms would be useful to make strategies for the genetic improvement for growth and carcass traits of local cattle.</p>

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Myostatin gene promoter: structure, conservation and importance as a target for muscle modulation

Cited by 37 publications

References 115 publications

The extracellular matrix phenome across species

The extracellular matrix phenome across species

Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition

Myostatin Gene as a Genetic Marker for Growth and Carcass Traits in Beef Cattle

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