Reticulon-1C Involvement in Muscle Regeneration.

Federica Rossin,Cesare Gargioli,Stefano Cannata,Ersilia Fornetti,Lucia Latella,Elena Avitabile,Giorgia Catarinella,Stefano Testa,Serafina Oliverio,Federica Di Sano

doi:10.3390/metabo11120855

Abstract

Skeletal muscle is a very dynamic and plastic tissue, being essential for posture, locomotion and respiratory movement. Muscle atrophy or genetic muscle disorders, such as muscular dystrophies, are characterized by myofiber degeneration and replacement with fibrotic tissue. Recent studies suggest that changes in muscle metabolism such as mitochondrial dysfunction and dysregulation of intracellular Ca2+ homeostasis are implicated in many adverse conditions affecting skeletal muscle. Accumulating evidence also suggests that ER stress may play an important part in the pathogenesis of inflammatory myopathies and genetic muscle disorders. Among the different known proteins regulating ER structure and function, we focused on RTN-1C, a member of the reticulon proteins family localized on the ER membrane. We previously demonstrated that RTN-1C expression modulates cytosolic calcium concentration and ER stress pathway. Moreover, we recently reported a role for the reticulon protein in autophagy regulation. In this study, we found that muscle differentiation process positively correlates with RTN-1C expression and UPR pathway up-regulation during myogenesis. To better characterize the role of the reticulon protein alongside myogenic and muscle regenerative processes, we performed in vivo experiments using either a model of muscle injury or a photogenic model for Duchenne muscular dystrophy. The obtained results revealed RTN-1C up-regulation in mice undergoing active regeneration and localization in the injured myofibers. The presented results strongly suggested that RTN-1C, as a protein involved in key aspects of muscle metabolism, may represent a new target to promote muscle regeneration and repair upon injury.

Highlights

Myogenic differentiation is an essential process of muscle development depending on the activity of different specific cells and environmental signals [1,2]
These results suggested the involvement of reticulon protein 1C (RTN-1C) in the muscle differentiation process
We investigated whether RTN-1C could affect endoplasmic reticulum (ER) stress response during Duchenne Muscular Dystrophy (DMD) pathogenesis

Summary

Introduction

Myogenic differentiation is an essential process of muscle development depending on the activity of different specific cells and environmental signals [1,2]. While the number of skeletal muscle fibers remains constant after achieving adulthood, skeletal muscle metabolism and mass are influenced by various factors such as diet, genetics, hormones, growth factors, and mechanical stimuli [3]. Loss of skeletal muscle mass is associated with a wide array of disease states such as aging, cancer, HIV, chronic heart failure, burn injury, etc. Myofiber degeneration is a common feature of genetic muscle disorders, such as muscular dystrophies, characterized by the myofibers’ replacement with fibrous and fat tissue [5]. Skeletal muscle contains an extremely extensive network of specialized endoplasmic reticulum (ER), namely sarcoplasmic reticulum. ER functional disturbance causes ER stress and leads to the accumulation of unfolded or misfolded proteins, thereby triggering the unfolded protein response (UPR) to alleviate cellular stress and re-establish homeostasis [6,7]

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Results

Conclusion