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The final goal of this project is to define the key signals between macrophages and endothelial progenitors and the relevance of this crosstalk in muscle development and diseases. We have indeed shown how the perturbation of this signaling triggers the phenomenon of endothelial to mesenchymal transition (EndMT): this can lead to impaired angiogenesis and the exacerbation of fibrosis, which represents a major obstacle for the success of other ongoing preclinical therapies for muscle genetic disease. We have also demonstrated that polarized macrophages directly modulate EndMT in endothelial progenitors. Indeed M2a and M2c macrophages appear to directly counteract TGF-β-induced EndMT. The action appears to be specific, since M0 and M1 do not influence these parameters. We are further characterizing this process by performing Next Generation Sequencing on the isolated endothelial progenitors in different EndMT-inducing conditions, to identify new therapeutic targets to be exploited to restore the homeostatic capacity of the tissue, breaking the vicious circle that leads to persistent inflammation/necrosis, defective neo-angiogenesis and eventual irreversible loss of tissue integrity and function.

The final goal of this project is to define the key signals between macrophages and endothelial progenitors and the relevance of this crosstalk in muscle development and diseases. We have indeed shown how the perturbation of this signaling triggers the phenomenon of endothelial to mesenchymal transition (EndMT): this can lead to impaired angiogenesis and the exacerbation of fibrosis, which represents a major obstacle for the success of other ongoing preclinical therapies for muscle genetic disease. We have also demonstrated that polarized macrophages directly modulate EndMT in endothelial progenitors. Indeed M2a and M2c macrophages appear to directly counteract TGF-β-induced EndMT. The action appears to be specific, since M0 and M1 do not influence these parameters. We are further characterizing this process by performing Next Generation Sequencing on the isolated endothelial progenitors in different EndMT-inducing conditions, to identify new therapeutic targets to be exploited to restore the homeostatic capacity of the tissue, breaking the vicious circle that leads to persistent inflammation/necrosis, defective neo-angiogenesis and eventual irreversible loss of tissue integrity and function.

(2017). Endothelial-mesenchymal transition and the immune system:an evolving paradigm in muscle fibrosis and heterotopic ossification.. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2017).

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