Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

Abstract BackgroundMyostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. ResultsA recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. ConclusionsFusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

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Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

10.21203/rs.2.19059/v5 ◽

2020 ◽

Author(s):

Gaoxiao Xu ◽

Ning Zhang ◽

Siying Liu ◽

Tingting Wei ◽

Xingfa Chen ◽

...

Keyword(s):

Growth Rate ◽

Growth Performance ◽

Muscle Mass ◽

Transforming Growth Factor ◽

Recombinant Adenovirus ◽

Muscle Growth ◽

Active Immunisation ◽

Gh Secretion ◽

Booster Immunisation ◽

Animal Growth

Abstract Background Myostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. Results A recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. Conclusions Fusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

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Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

10.21203/rs.2.19059/v6 ◽

2020 ◽

Author(s):

Gaoxiao Xu ◽

Ning Zhang ◽

Siying Liu ◽

Tingting Wei ◽

Xingfa Chen ◽

...

Keyword(s):

Growth Rate ◽

Growth Performance ◽

Muscle Mass ◽

Transforming Growth Factor ◽

Recombinant Adenovirus ◽

Muscle Growth ◽

Active Immunisation ◽

Gh Secretion ◽

Booster Immunisation ◽

Animal Growth

Abstract Background Myostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. Results A recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. Conclusions Fusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

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Adenovirus Virus Expressing Myostatin- Somatostatin Fusing Gene Promote the Growth Rate of the Mice

10.21203/rs.2.19059/v1 ◽

2019 ◽

Author(s):

Xinglong Wang ◽

Gaoxiao Xu ◽

Ning Zhang ◽

Xingfa Chen ◽

Dongling Yu

Keyword(s):

Immune Response ◽

Growth Rate ◽

Muscle Mass ◽

Recombinant Adenovirus ◽

Specific Immune Response ◽

Vaccine Antigen ◽

Inhibitory Effects ◽

Boost Immunization ◽

Animal Growth

Abstract Myostatin (MSTN) and somatostatin (SST) are negative regulate factors in the animals. Immunized animals with these proteins induce the related immune response, which could neutralize the normal inhibitory effects of these proteins. Since adenovirus was the mostly wildly used vector for delivering vaccine antigen, here, a recombinant adenovirus expressing MSTN-SST were constructed and mice were inoculated with the recombinant adenovirus. As our predicted, immunization with this adenovirus one time or two times were all induced the specific immune response and resulting in an improve growth rate and muscle mass. And boost immunization improved the effect of the immunization. Accordingly, adenovirus can be used as a vector for deliver myostatin and somatostatin gene, so as to increase animal growth rate and muscle mass of the animals.

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Adenovirus Virus Expressing Myostatin- Somatostatin Fusing Gene Promote the Growth Rate of the Mice

10.21203/rs.2.19059/v2 ◽

2020 ◽

Author(s):

Xinglong Wang ◽

Gaoxiao Xu ◽

Ning Zhang ◽

Xingfa Chen ◽

Dongling Yu

Keyword(s):

Immune Response ◽

Growth Rate ◽

Antibody Response ◽

Muscle Mass ◽

Recombinant Adenovirus ◽

Pathological Change ◽

Inhibitory Effects ◽

Booster Immunization ◽

Related Cell ◽

Animal Growth

Abstract Background Myostatin (MSTN) and somatostatin (SST) are all involved in regulation the growth of the animals. Animals immunized with these proteins induce the related immune response, which could neutralize the normal inhibitory effects of these two proteins. Here, a recombinant adenovirus expressing MSTN-SST was constructed and used to deliver these two antigen to mice, so as to check the immunize efficacy of these proteins delivered in this way. Results The adenovirus expression fusing protein MSTN-SST was successfully rescued on HEK293A cell as adenovirus related cell pathological change were observed after transfection with the adenovirus genome harboring MSTN-SST gene. The expression of MSTN-SST were confirmed using western blotting and indirect immunofluorescence. Immunization with the recombinant adenovirus once or twice were successfully induce immune response against MSTN-SST and resulted in an improved growth rate and muscle mass. In addition, a booster immunization leaded a better results shown as higher antibody response and mice growth rate. Conclusions Accordingly, adenovirus can be used as a vector for deliver myostatin and somatostatin gene to increase animal growth rate and muscle mass .

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GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1916034117 ◽

2020 ◽

Vol 117 (9) ◽

pp. 4910-4920 ◽

Cited By ~ 3

Author(s):

Joonho Suh ◽

Na-Kyung Kim ◽

Seung-Hoon Lee ◽

Je-Hyun Eom ◽

Youngkyun Lee ◽

...

Keyword(s):

Bone Mass ◽

Muscle Mass ◽

Transforming Growth Factor ◽

Bone Fractures ◽

Muscle Growth ◽

Transforming Growth Factor Β ◽

Biochemical Properties ◽

Bmp Signaling ◽

Morphogenetic Protein ◽

Perinatal Lethality

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.

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Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2019263117 ◽

2020 ◽

Vol 117 (49) ◽

pp. 30907-30917 ◽

Cited By ~ 1

Author(s):

Se-Jin Lee ◽

Adam Lehar ◽

Yewei Liu ◽

Chi Hai Ly ◽

Quynh-Mai Pham ◽

...

Keyword(s):

Family Member ◽

Muscle Mass ◽

Transforming Growth Factor ◽

Muscle Growth ◽

Functional Redundancy ◽

Activin A ◽

Metabolic Effects ◽

Type I ◽

Type Ii

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

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Smad2 and 3 transcription factors control muscle mass in adulthood

AJP Cell Physiology ◽

10.1152/ajpcell.00104.2009 ◽

2009 ◽

Vol 296 (6) ◽

pp. C1248-C1257 ◽

Cited By ~ 264

Author(s):

Roberta Sartori ◽

Giulia Milan ◽

Maria Patron ◽

Cristina Mammucari ◽

Bert Blaauw ◽

...

Keyword(s):

Transcription Factors ◽

Muscle Mass ◽

Drug Targets ◽

Transforming Growth Factor ◽

Muscle Growth ◽

Mammalian Target Of Rapamycin ◽

Ring Finger ◽

Transforming Growth Factor Β ◽

Control Muscle

Loss of muscle mass occurs in a variety of diseases, including cancer, chronic heart failure, aquired immunodeficiency syndrome, diabetes, and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis, and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover, recent results confirm that other transforming growth factor-β (TGF-β) members control muscle mass. Using genetic tools, we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF-β and induce an atrophy program that is muscle RING-finger protein 1 (MuRF1) independent. Furthermore, Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mammalian target of rapamycin (mTOR) signaling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation, especially when they are combined with IGF-1-Akt activators.

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A Novel Nanobody Directed against Ovine Myostatin to Enhance Muscle Growth in Mouse

Animals ◽

10.3390/ani10081398 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1398

Author(s):

Kepeng Ou ◽

Youjian Li ◽

Peng Wu ◽

Jixing Guo ◽

Xiujing Hao ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Intramuscular Injection ◽

Transforming Growth Factor ◽

Muscle Growth ◽

Domestic Animals ◽

Negative Regulator ◽

Promising Treatment ◽

Animal Growth ◽

Growth Factor Beta ◽

Diagnostics And Therapy

Myostatin (MSTN) is a member of the transforming growth factor beta superfamily and is a negative regulator of myogenesis. It has been shown to function by controlling the proliferation of myoblasts. MSTN inhibition is considered as a promising treatment for promoting animal growth in livestock. Nanobodies, a special antibody discovered in camel, have arisen as an alternative to conventional antibodies and have shown great potential when used as tools in different biotechnology fields, such as diagnostics and therapy. In this study, we examined the effect of MSTN inhibition by RMN on the muscle growth of mice. The results showed that RMN could specifically detect and bind MSTN, as well as inhibit MSTN activity. A significant increase in skeletal muscle mass was observed after intramuscular injection of RMN into mice. Enhanced muscle growth occurred because of myofiber hypertrophy. These results offer a promising approach to enhance muscle growth that warrants further investigation in domestic animals.

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Changing Composition and Growth Performance of Services Sector in India after Liberalization

Indian Journal of Economics and Development ◽

10.35716/ijed/ns20-012 ◽

2020 ◽

pp. 432-436

Keyword(s):

Growth Rate ◽

Growth Performance ◽

Direct Investment ◽

Service Sector ◽

World Market ◽

Limiting Factor ◽

Arunachal Pradesh ◽

Services Sector ◽

State Economy ◽

The World

This present study makes an analysis of changing contribution of sub-sector and composition and growth performance in Indian economy. In addition to that, the contribution of sub-sector of service sector in state economy. The results revealed that the growth rate of Chandigarh was high due to providing especial emphasis on dominating sub-sectors of services and its most preferred destination for technology whereas, Sikkim and Arunachal Pradesh due to geographical and environmental conditions development were higher in floriculture and agriculture, although, tourism emerged as a new profession and have different opportunities. Apart of that, in the wake of some challenges in the form of lack of infrastructure, recent crisis in the world market, foreign direct investment (FDI) restrictions and outsourcing backlash were major limiting factor.

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