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

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...

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Main Authors: Rocco Bernasconi, Kerstin Thriene, Elena Romero‐Fernández, Christine Gretzmeier, Tobias Kühl, Mareike Maler, Pauline Nauroy, Svenja Kleiser, Anne‐Catherine Rühl‐Muth, Michael Stumpe, Dimitra Kiritsi, Stefan F Martin, Boris Hinz, Leena Bruckner‐Tuderman, Jörn Dengjel, Alexander Nyström
Format: Article
Language:English
Published: Springer Nature 2021-08-01
Series:EMBO Molecular Medicine
Subjects:
collagen VII
genetic disease
inflammation
skin
therapy
Online Access:https://doi.org/10.15252/emmm.202114392
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Summary: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 that 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 of Ang‐(1‐7) efficiently attenuated progression of multi‐organ fibrosis and increased survival of RDEB mice. Collectively, our study shows that selective down‐modulation of pro‐inflammatory immunity may mitigate injury‐induced fibrosis. Furthermore, together with published data, our data highlight molecular diversity among fibrotic conditions. Both findings have direct implications for the design of therapies addressing skin fragility and fibrosis.
ISSN:1757-4676
1757-4684

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