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Regeneration or fibrosis of injured tissue: macrophages lead the way

After an injury, many tissues often develop fibrosis[1], which can be disabling. An international team involving researchers from CEA-Jacob has now identified a key player in the fibrosis development: macrophages [2]. These observations pave the way for targeted treatments.

Published on 2 April 2020

Skin wounds often lead to fibrotic scars but can, in rare cases, lead to a beneficial regenerative repair response.

Using a mouse model mimicking repair of a skin wound, researchers from CEA-Jacob, Inserm, CNRS and several French, German and American universities, have characterized the cellular and molecular events that regulate the balance between fibrotic repair and tissue regeneration and have identified a key player in this balance: macrophages. In fact, macrophages, known to be essential in the initial stages of tissue repair can induce a fibrotic process if they are not disposed of at the late stages of skin wound repair. Indeed, if not disposed of, macrophages phagocyte and degrade an inhibitor of a major metabolic pathway, the Wnt pathway, leading to chronic activation of this pathway and skin fibrosis. Suppression of this macrophage mediated phagocytosis is sufficient to reverse the balance between fibrosis and skin regeneration. Macrophages can therefore modify the healing fate of skin wounds.

In human, this team has shown that, in a skin pathology, Suppurated Hidradenitis (a chronic, recurrent and incapacitating skin condition), phagocytosis of the Wnt pathway inhibitor by macrophages is correlated with wound repair associated with fibrosis. These results indicate that the characterized mechanism indicates therapeutic target that can be used to promote skin regeneration instead of fibrosis.

François Jacob Institute of biology - CEA
Paris-Diderot University
​Paris-Sud University
​Center for Complex Biological Systems, University of California
​University Leipzig Medical Center
​School of Medicine, New York University
​Charles River Laboratories
​Cohen Children's Medical Center Northwell Health, New Hyde Park
​DFG-German Research Council Transregio 67
​Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris

[1] Fibrosis is the transformation of body tissue into fibrous tissue that has lost the properties of the original tissue.
[2] Macrophages are cells that can infiltrate from blood or are found resident in tissues. During the inflammatory response, their role includes the removal of cellular debris and pathogens.

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