Inflammation is a normal response of the body to infections and injury. The migration into the inflamed tissue of some cells of our immune system known as macrophages is a requisite for the elimination of cell debris and the subsequent regeneration of injured tissues. Tissue regeneration most often involves the activation of “stem cells” that are normally in a quiescent stage. We found that a protein named ZEB1 both protects skeletal muscle from damage and is required for its regeneration. ZEB1 promotes the transition of macrophages toward an anti-inflammatory and pro-regenerative status in acute and chronic (muscular dystrophies) injured skeletal muscles. ZEB1 is also required for muscle stem cells to maintain their quiescent status. These results established ZEB1 as an important factor in the regulation of inflammatory response and in improving the regenerative capacity of stem cells, opening new avenues in the treatment of muscular dystrophies (Siles et al., 2019). However, continuous inflammation is at the root of many diseases. Thus, chronic inflammation of some tissues, such as the liver, pancreas or colon, is a known risk factor for the development of cancer. We found that ZEB1 is required for the inflammation of the colon. We found that, contrary to what occurs in skeletal muscle, ZEB1 promotes (rather than inhibits) chronic inflammation and its progression toward cancer. ZEB1 causes the inflammation of the epithelial cells in the colon (a disease known as ulcerative colitis) and contributes to their subsequent transformation into cancer cells. ZEB1 triggers inflammation by inducing lesions in the DNA of the cell but also by inhibiting our body’s self-repair mechanisms as it prevents the repair of DNA lesions through the inhibition of an enzyme called MPG. This work unveils a new mechanism in the link between inflammation and cancer and can help to develop new strategies in the treatment of ulcerative colitis and of other chronic inflammatory conditions that are risk factors in cancer development (de Barrios et al 2019).
Reference
Siles L, Ninfali C, Cortes M, Darling DS & Postigo A * (2019), ‘ZEB1 protects skeletal muscle from damage and is required for its regeneration’. Nature Communications. 10:1364. (*corresponding author). Impact Factor: 12.3
de Barrios O, Sanchez-Moral L, Cortés M, Ninfali C, Profitós-Pelejà N, Martinez-Campanario MC, Siles L, del Campo R, Fernández-Aceñero MJ, Darling DS, Castells A, Maurel J, Salas A, Dean DC & Postigo A * (2019) ‘ZEB1 promotes inflammation and progression towards inflammation-driven carcinoma through repression of the DNA repair glycosylase MPG in epithelial cells.’ Gut. 68:2129- 41 (* corresponding author). Impact Factor: 17.9. Highlighted by the journal with a video Abstract
ZEB1 increases in the undamaged fibers of injured skeletal muscles
