Pro-inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang-(1-7)

ABSTRACT: Recessive dystrophic epidermolysis bullosa (RDEB), a genetic skin blistering disease, is a paradigmatic condition of tissue fragility-driven multi-organ fibrosis. Here, longitudinal analyses of the tissue proteome through the course of naturally developing disease in RDEB mice revealed that increased pro-inflammatory immunity associates with fibrosis evolution. Mechanistically, this fibrosis is a consequence of altered extracellular matrix organization rather than of increased abundance of major structural proteins. In a humanized system of disease progression, we targeted inflammatory cell-fibroblast communication with Ang-(1-7) - an anti-inflammatory heptapeptide of the renin-angiotensin system, which reduced the fibrosis-evoking aptitude of RDEB cells. In vivo, systemic administration o

SUBMITTER: Dr. Rocco Bernasconi 

PROVIDER: S-SCDT-EMM-2021-14392 | biostudies-other |

REPOSITORIES: biostudies-other