Control of fibrosis by TGFβ signalling modulation promotes redifferentiation during limited regeneration of mouse ear.

Transforming growth factor beta (TGFβ) signalling is involved in several aspects of regeneration in many organs and tissues of primitive vertebrates. It has been difficult to recognize the role of this signal in mammal regeneration due to the low ability of this animal class to reconstitute tissues. Nevertheless, ear-holes in middle-age female mice represent a model to study the limited epimorphic-like regeneration in mammals. Using this model, in this study we explored the possible participation of TGFβ signalling in mammal regeneration. Positive pSmad3 cells, as well as TGFβ1 and TGFβ3 isoforms, were detected during the redifferentiation phase in the blastema-like structure. Daily administration of the inhibitor of the TGFβ intracellular pathway, SB431542, during 7 days from the re-differentiation phase, resulted in a decreased level of pSmad3 accompanied by a transitory higher growth of the new tissue, larger cartilage nodules, and new muscle formation. These phenotypes were associated with a decrease in the number of α-SMA-positive cells and loose packing of collagen I. These results indicate that the modulation of the fibrosis mediated by TGFβ signalling contributes to enhancing the differentiation of cartilage and muscle during limited ear-hole regeneration.