Pro-inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang-(1-7).
collagen VII
genetic disease
inflammation
skin
therapy
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
revised:
19
07
2021
received:
07
04
2021
accepted:
23
07
2021
pubmed:
31
8
2021
medline:
26
10
2021
entrez:
30
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34459121
doi: 10.15252/emmm.202114392
pmc: PMC8495454
doi:
Substances chimiques
Collagen Type VII
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14392Subventions
Organisme : CIHR
ID : 375597
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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