A new study by Spanish researchers describes a new mechanism of muscle repair after physiological damage based on the rearrangement of the nuclei of muscle fibers and independently of muscle stem cells.
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 the Pompeu Fabra University (UPF, Spain) / Centro Nacional de Investigationes Cardiovasculares (CNIC, Spain) / CIBERNED (Spain) and the Instituto de Medicina Molecular João Lobo Antunes (iMM, Portugal), published on October 15 in the journal Science, describes a new mechanism of muscle repair after physiological damage based 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 few decades, most studies have focused on mechanisms involving multiple cells, including muscle stem cells, that 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 during injury, nuclei are attracted to the damaged site, accelerating repair of contractile units. Next, the team dissected the molecular mechanism behind this observation: “Our experiments with muscle cells in the laboratory showed that movement of nuclei to sites of injury results 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. “This self-repairing process of muscle fibers occurs rapidly in mice and humans after exercise-induced muscle injury, and therefore represents an effective protective mechanism in terms of 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 the 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: “This discovery constitutes an important advance in the understanding of muscle biology, physiology (including physiology exercise) and muscle dysfunction.
Reference: “Muscle repair after physiological damage relies on nuclear migration for cell reconstruction” by William Roman, Helena Pinheiro Mafalda R. Pimentel, Jessica Segalés, Luis M. Oliveira, Esther García-Domínguez, Mari Carmen Gómez-Cabrera, Antonio L. Serrano, Edgar R. Gomes and Pura Muñoz-Cánoves, October 15, 2021, Science.
DOI: 10.1126 / science.abe5620
The work was carried out at UPF / CNIC / CIBERNED and at iMM in collaboration with the University of Valencia / INCLIVA.
This study was funded by the European Research Council, the French Association against Myopathies, the European Organization for Molecular Biology, the Human Frontiers Science Program and the Spanish Ministry of Science.
Pompeu Fabra University (Spain)
The UPF (and the CEXS Department in particular) and the CNIC are two centers of excellence (respectively María de Maeztu and Severo Ochoa) devoted to research in Biomedicine and Cardiovascular.
The Center for Biomedical Research Network on Neurodegenerative Diseases (CIBERNED) is a research organization founded by the Spanish government to merge basic and clinical research targeting pathologies of great importance to the national health system.
Instituto de Medicina Molecular (iMM, Portugal)
The iMM – Instituto de Medicina Molecular João Lobo Antunes is a leading Portuguese non-profit private research institute that offers a dynamic scientific environment, aimed at nurturing innovative ideas in basic, clinical and translational biomedical research.
The Centro Nacional de Investigaciones Cardiovasculares (CNIC), led by Dr Valentín Fuster, is dedicated to cardiovascular research and translating the knowledge gained into real benefits for patients. The CNIC, recognized by the Spanish government as a Severo Ochoa center of excellence, is funded through a pioneering public-private partnership between the government (through the Carlos III Health Institute) and the Pro-CNIC Foundation, which brings together 12 of the most important Spanish private companies.