New muscle repair mechanism revealed

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Muscle is known to regenerate itself through a complex process that involves several steps and relies on stem cells. Now, a new study led by researchers from UPF, Centro Nacional de Investigationes Cardiovasculares (CNIC), CIBERNED and Instituto de Medicina Molecular João Lobo Antunes (iMM, Portugal), published on October 15 in the journal Science, describes a new mechanism for muscle repair after physiological damage relying on the rearrangement of the nuclei of muscle fibers, and independently of muscle stem cells. This protective mechanism paves the way for a broader understanding of muscle repair in physiology and disease.

Skeletal muscle tissue, the organ responsible for locomotion, is made up of cells (fibers) that have more than one nucleus, a feature almost unique to our body. Despite the plasticity of these fibers, their contraction can be associated with muscle damage. William Roman, first author of the study and researcher at UPF, explains: “Even under physiological conditions, regeneration is vital for the muscle to withstand the mechanical stress of contraction, which often leads to cell damage”. Although muscle regeneration has been studied extensively over the past decades, most studies have focused on mechanisms involving multiple cells, including muscle stem cells, which are needed when significant muscle damage occurs ”.

“In this study, we found an alternative muscle tissue repair mechanism that is autonomous in muscle fibers,” explains Pura Muñoz-Cánoves, professor at ICREA and principal investigator at UPF and CNIC, and responsible for the ‘study. The researchers (including Antonio Serrano (UPF) and Mari Carmen Gómez-Cabrera (University of Valencia and INCLIVA) used different in vitro injury models and exercise models in mice and humans to observe that in cases of injury, the nuclei are attracted to the damaged site, accelerating the repair of contractile units. Next, the team dissected the molecular mechanism for this observation: “Our experiments with muscle cells in the laboratory showed that the movement of nuclei towards them. Injury sites resulted in local delivery of mRNA molecules. These mRNA molecules are translated into proteins at the injury site to act as building blocks for muscle repair, “explains William Roman. Self-repair of muscle fibers occurs rapidly in both mice and humans after exercise-induced muscle injury, and therefore represents an economical protective mechanism. me in time and energy for the repair of minor lesions, ”adds Pura Muñoz-Cánoves.

In addition to its implications for muscle research, this study also introduces more general concepts for cell biology, such as the movement of nuclei to sites of injury. “One of the most fascinating things about these cells is the movement during the development of their nuclei, the largest organelles inside the cell, but the reasons why nuclei move are largely unknown. . Now we have shown a functional relevance for this phenomenon in adulthood during cell repair and regeneration ”, explains Edgar R. Gomes, group leader at the Instituto de Medicina Molecular and professor at the Faculty of Medicine of the University of Lisbon, which co-led the study.

On the importance of these discoveries, Pura Muñoz-Cánoves, Antonio Serrano and Mari Carmen Gómez-Cabrera agree that: “This discovery constitutes an important advance in the understanding of muscle biology, physiology (including physiology of exercise) and muscle dysfunction ”.

Reference: Roman W, Pinheiro H, Pimentel MR, et al. Muscle repair after physiological damage relies on nuclear migration for cell reconstruction. Science. 2021; 374 (6565): 355-359. doi: 10.1126 / science.abe5620

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