Abstract
Muscle regeneration involves the activation of satellite cells, is regulated at the genetic and epigenetic levels, and is strongly influenced by gene activation and environmental conditions. The aim of this study was to determine whether the overexpression of mIGF-1 can modify functional features of satellite cells during the differentiation process, particularly in relation to modifications of intracellular Ca2+ handling.Satellite cells were isolated from wild-type and MLC/mIGF-1 transgenic mice. The cells were differentiated in vitro, and morphological analyses, intracellular Ca2+ measurements, and ionic current recordings were performed.mIGF-1 overexpression accelerates satellite cell differentiation and promotes myotube hypertrophy. In addition, mIGF-1 overexpression-induced potentiation of myogenesis triggers both quantitative and qualitative changes to the control of intracellular Ca2+ handling. In particular, the differentiated MLC/mIGF-1 transgenic myotubes have reduced velocity and amplitude of intracellular Ca2+ increases after stimulation with caffeine, KCl and acetylcholine. This appears to be due, at least in part, to changes in the physico-chemical state of the sarcolemma (increased membrane lipid oxidation, increased output currents) and to increased expression of dihydropyridine voltage-operated Ca2+ channels. Interestingly, extracellular ATP and GTP evoke intracellular Ca2+ mobilization to greater extents in the MLC/mIGF-1 transgenic satellite cells, compared to the wild-type cells.These data suggest that these MLC/mIGF-1 transgenic satellite cells are more sensitive to trophic stimuli, which can potentiate the effects of mIGF-1 on the myogenic programme.
Highlights
Insulin-like growth factors (IGFs) represent a system of circulating and/or locally secreted factors that have key roles in cell growth, differentiation and regeneration
In particular we observed that myosin light chain (MLC)/mIGF-1 transgenic mousederived cells, compared to wild-type cell cultures, showed: i) a higher myogenic differentiation (Fig. 1c), ii) a higher fusion index (quantified as the percentage of Hoechst-stained nuclei located within multinucleated cells, positive to sarcomeric myosin, and calculated on the total analysed MyoD-positive nuclei (Fig. 1d), and iii) a myonuclear accretion
It has been previously demonstrated that mIGF-1 gene expression induces local skeletal muscle hypertrophy, which improves muscle mass and strength by activating calcineurinmediated Ca2+ signalling and GATA-2/NF-ATc1 [11]
Summary
Insulin-like growth factors (IGFs) represent a system of circulating and/or locally secreted factors that have key roles in cell growth, differentiation and regeneration. IGF-1 has a critical role in activation, proliferation and differentiation of muscle stem cells (satellite cells), and in tissue repair [1,2,3] During this process, mIGF-1 triggers the activation of in situ satellite cells, stimulates the recruitment of circulating stem cells, modulates inflammatory responses, and reduces fibrosis. Several processes that are modulated by mIGF-1 have been studied and described in myosin light chain (MLC)/mIGF-1 transgenic mice, an animal model in which the mIGF-1 gene is regulated by the MLC promoter. This restricts the expression of the transgene selectively to skeletal muscle, and predominantly in muscle with a high ratio of fast-twitch fibres [7]. The localized up-regulation of mIGF-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle [4,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
