Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis

Ronzoni, Flavio Lorenzo; Ceccarelli, Gabriele; Perini, Ilaria; Benedetti, Laura; Galli, Daniela; Mulas, Francesca; Balli, Martina; Magenes, Giovanni; Bellazzi, Riccardo; Angelis, Gabriella Cusella De; Sampaolesi, Maurilio

doi:10.2174/1389201018666170201124602

Cited by 8 publications

(9 citation statements)

References 25 publications

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“…In particular, embryonic stem cells and reprogrammed fibroblasts would represent the best tool for therapy if their capacity to form teratoma could be abolished. On the other side, the use of adult progenitors is limited by the reduced plasticity of the cells, although the exposure to recombinant proteins can improve their myogenic differentiation potential [39][40][41][42][43]. So far, data on the injection of adult satellite stem cells and the influence of new neuro-muscular junction formations are limited.…”

Section: Discussionmentioning

confidence: 99%

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization

Ronzoni

Giarratana

Crippa

et al. 2021

IJMS

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Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.

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Section: Discussionmentioning

confidence: 99%

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization

Ronzoni

Giarratana

Crippa

et al. 2021

IJMS

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“…A synthetic MET agonist with structural similarity to native HGF causes the phosphorylation and activation of AKT1 in C2C12 myoblasts that results in increased fusion and myotube size (Cassano et al, 2008;Perini et al, 2015). Injection of the MET agonist into skeletal muscle or transgenic expression of the protein in skeletal muscle increases fiber cross-sectional area and improves exercise performance (Ronzoni et al, 2017). The decreased number of myogenin positive nuclei and absence of an effect on myoblast fusion point to a delay in the differentiation program in response to HGF.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor acts as a mitogen for equine satellite cells via protein kinase C δ–directed signaling

Brandt

Kania

Gonzalez

et al. 2018

Journal of Animal Science

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Hepatocyte growth factor (HGF) signals mediate mouse skeletal muscle stem cell, or satellite cell (SC), reentry into the cell cycle and myoblast proliferation. Because the athletic horse experiences exercise-induced muscle damage, the objective of the experiment was to determine the effect of HGF on equine SC (eqSC) bioactivity. Fresh isolates of adult eqSC were incubated with increasing concentrations of HGF and the initial time to DNA synthesis was measured. Media supplementation with HGF did not shorten (P > 0.05) the duration of G0/G1 transition suggesting the growth factor does not affect activation. Treatment with 25 ng/mL HGF increased (P < 0.05) eqSC proliferation that was coincident with phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and AKT serine/threonine kinase 1 (AKT1). Chemical inhibition of the upstream effectors of ERK1/2 or AKT1 elicited no effect (P > 0.05) on HGF-mediated EdU incorporation. By contrast, treatment of eqSC with 2 µm Gö6983, a pan-protein kinase C (PKC) inhibitor, blocked (P < 0.05) HGF-initiated mitotic activity. Gene expression analysis revealed that eqSC express PKCα, -δ and -ε isoforms. Knockdown of PKCδ with a small interfering RNA (siRNA) prevented (P > 0.05) HGF-mediated EdU incorporation. The siPKCδ was specific to the kinase and did not affect (P > 0.05) expression of either PKCα or PKCε. Treatment of confluent eqSCs with 25 ng/mL HGF suppressed (P < 0.05) nuclear myogenin expression during the early stages of differentiation. These results demonstrate that HGF may not affect activation but can act as a mitogen and modest suppressor of differentiation.

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“…It is an emerging fact that adult stem cells [ 6 , 7 ] can be involved in miRNA regulation by secreting miRNA-containing exosomes, extracellular vesicles with nanoscale bilayer membranes. Indeed, exposure to specific miRNA combinations can boost the myogenic differentiation of stem cells [ 8 , 9 ] and skeletal muscle tumor cells [ 10 ]. The aberrant expression of miRNAs is thought to be closely associated with the progression of different muscle-wasting disorders.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Implications of miRNAs for Muscle-Wasting Conditions

Yedigaryan

Sampaolesi

2021

Cells

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MicroRNAs (miRNAs) are small, non-coding RNA molecules that are mainly involved in translational repression by binding to specific messenger RNAs. Recently, miRNAs have emerged as biomarkers, relevant for a multitude of pathophysiological conditions, and cells can selectively sort miRNAs into extracellular vesicles for paracrine and endocrine effects. In the overall context of muscle-wasting conditions, a multitude of miRNAs has been implied as being responsible for the typical dysregulation of anabolic and catabolic pathways. In general, chronic muscle disorders are associated with the main characteristic of a substantial loss in muscle mass. Muscular dystrophies (MDs) are a group of genetic diseases that cause muscle weakness and degeneration. Typically, MDs are caused by mutations in those genes responsible for upholding the integrity of muscle structure and function. Recently, the dysregulation of miRNA levels in such pathological conditions has been reported. This revelation is imperative for both MDs and other muscle-wasting conditions, such as sarcopenia and cancer cachexia. The expression levels of miRNAs have immense potential for use as potential diagnostic, prognostic and therapeutic biomarkers. Understanding the role of miRNAs in muscle-wasting conditions may lead to the development of novel strategies for the improvement of patient management.

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Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis

Cited by 8 publications

References 25 publications

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization

Hepatocyte growth factor acts as a mitogen for equine satellite cells via protein kinase C δ–directed signaling

Therapeutic Implications of miRNAs for Muscle-Wasting Conditions

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