January 26, 2023

New Mechanism Discovered for Muscle Regeneration

In spite of the plasticity of muscle cells, their contraction can be accompanied by muscle damage. Muscle regrowth has been deeply investigated in the past decades, a lot of studies were focused on mechanisms involving other cells, including muscle stem cells, which are required upon comprehensive muscle damage.
On the significance of these discoveries, Pura Muñoz-Cánoves says: “This finding constitutes a crucial advance in the understanding of muscle biology, in physiology and muscle dysfunction.”

The microtubule network (green) re-organizes at the muscle sore and brings in myonuclei. Credit: William Roman, iMM
Muscle is known to restore through a complicated procedure that depends and includes several actions on stem cells. Now, a new research study led by scientists at the Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal) and the University Pompeu Fabra (UPF Barcelona; Spain) and published on October 15, 2021, in the clinical journal Science describes a new system for muscle regrowth after physiological damage relying on the rearrangement of nuclei. This protective mechanism opens the road to a broader understanding of muscle repair work in physiology and illness.
Skeletal muscle tissue, the organ accountable for locomotion, is formed by cells that have more than one nucleus, an almost distinct function in our body. Despite the plasticity of muscle cells, their contraction can be accompanied by muscle damage. William Roman, main author of the research study and researcher at iMM and UPF Barcelona, explains: “Even in physiological conditions, regrowth is crucial for muscle to sustain the mechanical stress of contraction, which often leads to cellular damage.” Although muscle regeneration has actually been deeply investigated in the past decades, most studies were fixated mechanisms including other cells, including muscle stem cells, which are needed upon comprehensive muscle damage.
” In this research study, we found an alternative system of regeneration that is muscle cell self-governing,” states Pura Muñoz-Cánoves, group leader at the University Pompeu Fabra, and study leader. Researchers used different in vitro models of injury and models of workout in humans and mice to observe that upon injury, nuclei are attracted to the damage site, accelerating the repair work of the contractile systems. Next, the team dissected the molecular mechanism of this observation: “Our experiments with muscle cells in the laboratory revealed that the movement of nuclei to injury websites resulted in local shipment of mRNA particles. These mRNA particles are equated into proteins at the site of injury to serve as foundation for muscle repair,” explains William Roman. On the value of these discoveries, Pura Muñoz-Cánoves says: “This finding constitutes an essential advance in the understanding of muscle biology, in physiology and muscle dysfunction.”

In addition to its implications for muscle research study, this research study also presents more basic concepts for cell biology, such as the nuclear movement to injury websites. “One of the most remarkable things in these cells is the motion during advancement of their nuclei, the most significant organelles inside the cell, however the reasons nuclei move are mainly unknown. Now, we showed a practical importance for this phenomenon in their adult years throughout cellular repair work and regeneration,” says Edgar R. Gomes, group leader at the Instituto de Medicina Molecular and Professor at Faculdade de Medicina da Universidade de Lisboa, who co-led the research study.
Recommendation: “Muscle repair after physiological damage counts on nuclear migration for cellular 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, 15 October 2021, Science.DOI: 10.1126/ science.abe5620.
The work was established at iMM and UPF Barcelona in collaboration with the University of Valencia. This research study was funded by the Association Française contre les Myopathies, the European Molecular Biology Organization, the Human Frontiers Science Program, MINECO-Spain and the European Research Council.

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