The skin is the first line of defence to protect the body from dehydratation, injury and infection. The epidermis, the outer covering of the skin, is maintained throughout life by stem cells. The Rosenthal group has recently reported that a local isoform o f IGF-1 (mIGF-1) is able to enhance both skeletal muscle and heart regeneration, inducing the proliferation of a specific cell population in the bone marrow and enhancing their recruitment to the site of injury and their fusion with existing myocytes. In t his context, we will study the effect of specific expression of mIGF-1 in the epidermis by generating transgenic mice expressing mIGF-1 in a tissue specific and inducible manner.
We will compare the gene expression profiles of the mIGF-1 expressing skin with the data on m-IGF-expressing muscle already available, to see how much of the muscle regenerative response is recapitulated in the epidermis. After analysing the action of mIGF-1 on the regeneration and proliferative capacity of the skin, we will identify the molecules mediating such an effect, mainly focusing on the capacity of mIGF-1 to modify the secretion of growth factors and cytokines that may regulate the behaviour of surrounding cells. We will determine whether mIGF-1 expression results in increased stem cell proliferation in vivo, whether mIGF-1 enhances the recruitment of epidermal stem cells to the site of injury and will determine the capacity of these stem cells to differentiate and engraft different tissues. We will analyse the ability of epidermal mIGF-1 to interfere with scar formation or to enhance extra cellular matrix destruction and will study the effect of mIGF-1 expression on skin aging.
Finally, we will study whether mIGF-1 expression in the epidermis protects mice from developing immune-associated skin diseases. The proposed goals fulfil the program's requirements for human mobility, transfer of knowledge, gender balance and multidisciplinary approach.
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