title: Transient inactivation of myostatin induces muscle hypertrophy and overcompensatory growth in zebrafish via inactivation of the SMAD signaling pathway.
abstract: Myostatin (MSTN) is the main negative regulator of muscle growth and development in vertebrates. In fish, little is known about the molecular mechanisms behind how MSTN inactivation triggers skeletal muscle enhancement, particularly regarding the signaling pathways involved in this process. Moreover, there have not been reports on the biotechnological applications of MSTN and its signal transduction. In this context, zebrafish underwent compensatory growth using fasting and refeeding trials, and MSTN activity was inactivated with dominant negative LAPD76A recombinant proteins during the refeeding period, when a rapid, compensatory muscle growth was observed. Treated fish displayed an overcompensation of growth characterized by higher muscle hypertrophy and growth performance than constantly fed, control fish. Treatment with LAPD76A recombinant proteins triggered inactivation of the SMAD signaling pathway in skeletal muscle, the main signal transduction used by MSTN to achieve its biological actions. Therefore, transient inactivation of MSTN during the compensatory growth of zebrafish led to a decrease in the SMAD signaling pathway in muscle, triggering muscle hypertrophy and finally improving growth performance, thus, zebrafish achieved an overcompensation of growth. The present study shows an attractive strategy for improving muscle growth in a fish species by mixing a classical strategy, such as compensatory growth, and a biotechnological approach, such as the use of recombinant proteins for inhibiting the biological actions of MSTN. The mix of both strategies may represent a method that could be applied in order to improve growth in commercial fish of interest for aquaculture.
authors.affiliation: Universidad Andres Bello, Departmento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Av. Republica 217, Santiago, Chile; FONDAP, Interdisciplinary Center for Aquaculture Research (INCAR), Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago, Chile. Electronic address: edua.fuentes@uandresbello.edu.
authors.forename: Eduardo N
authors.initials: EN
authors.lastname: Fuentes
authors.forename: Katherine
authors.initials: K
authors.lastname: Pino
authors.forename: Cristina
authors.initials: C
authors.lastname: Navarro
authors.forename: Iselys
authors.initials: I
authors.lastname: Delgado
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Valdés
authors.forename: Alfredo
authors.initials: A
authors.lastname: Molina
mesh_terms: D000818:Animals; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D055435:Myostatin; D011994:Recombinant Proteins; D051785:Smad Proteins
keywords: Nutritional status; SMAD signaling pathways; Skeletal muscle growth; Zebrafish