A protein involved in cancer protects against muscle diseases

Researchers from the IDIBAPS Research Institute have found that the protein known as ZEB1 have beneficial or deleterious effects depending on its levels and the tissue where is expressed. Previous studies from the same group had shown that the uncontrolled increase of ZEB1 contributes to the development of different types of cancers. However, the new studies from the group show that ZEB1 protects the muscle from atrophy and muscular dystrophy.

The research, that has used both human samples and animal models, has been published in two articles in the journals Nature Communications and Nucleic Acids Research. The first authors of these works are Laura Siles and Chiara Ninfali, respectively, researchers in muscular pathology at IDIBAPS.

ZEB1 is essential to maintain a healthy muscle

Using samples from patients with Duchenne Muscular Dystrophy, a rare disease that begins in childhood and results in the progressive destruction of muscles, and experimental mouse models, the two papers show that ZEB1 is essential to protect the muscle of different diseases that cause damage or muscular atrophy. Conversely, a decrease in ZEB1 makes the muscles more susceptible to these pathologies.

In response to acute injury and in Duchenne's disease the muscle is damaged and it is necessary that their stem cells are activated to repair the injury. "The results obtained show that ZEB1 is necessary to reduce inflammation in the muscle and for the stem cells to repair it after an injury or in muscular dystrophy," explains Laura Siles.

On the other hand, in numerous clinical and pathological conditions (immobilization, aging, spinal cord injuries), there is a reduction in the volume of muscles in a process known as muscular atrophy. "The results obtained in the study have shown that ZEB1 protects the muscle from atrophy induced by immobilization or disuse," says Chiara Ninfali.

These works reveal an unexpected role for ZEB1, beyond cancer, and can open new strategies in the treatment of muscular dystrophies and situations that lead to a loss of muscle mass.

The study has been funded by various agencies, mainly by the Duchenne Parent Project Foundation and the Agency for Management of University and Research Grants (AGAUR) of the Generalitat de Catalunya.

In the image: Picture of a regenerating muscle following injury

Reference to the Articles:

ZEB1 protects skeletal muscle from damage and is required for its regeneration Siles L et al. Nature Communications. March 25, 2019. 10:1364. doi: 10.1038/s41467-019-08983-8

Regulation of muscle atrophy-related genes by the opposing transcriptional activities of ZEB1/CtBP and FOXO3 Ninfali C et al. Nucleic Acids Res, November 16, 2018. 46(20):10697-708. doi: 10.1093/nar/gky835