Comparing injury response pathways in regenerative and non-regenerative mammalian tissue to identify the divergence in regenerative potential

Most mammals, including humans, fail to regenerate many tissues. One barrier to regeneration may be the formation of scar tissue. Through comparisons between animals that regenerate and those that do not, research could identify divergences in response to injury, including the initiation of scar tissue formation. The African Spiny mouse, Acomys, offers a mammalian model of regeneration as it does not form scar tissue, and instead regrows many tissues after injury. To identify events that enable tissue regeneration, our research compared Acomys with Mus, a mouse species that does not show the same regenerative capacity or absence of scar tissue. Since Mus undergoes fibrosis while Acomys does not, these experiments examined an in vitro system of primary dermal fibroblasts to identify differences that occur at the molecular level of the cells involved in fibrosis. Thrombin, an enzyme elevated with wounding and associated with triggering regeneration, was used as a signal of injury to the fibroblasts. We conducted differential screens to analyze thrombin’s effect on proteins involved in cell growth, differentiation, proliferation, and scar tissue formation. Qualitatively, ERK, a protein that helps in the expression of growth related proteins, showed more rapid localization and greater intensity in Acomys compared to Mus, but only one protein, Sox-9, showed a statistically significant difference in Acomys after thrombin treatment. This research could reveal important divergences in regenerative potential among mammals, and offers an approach that might identify treatments to stimulate new tissue growth.