Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1.
Caveolin-1
adipogenesis
fibrosis
mesenchymal stem cells
scleroderma
Journal
Journal of scleroderma and related disorders
ISSN: 2397-1991
Titre abrégé: J Scleroderma Relat Disord
Pays: England
ID NLM: 101685427
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
15
06
2018
accepted:
02
12
2018
entrez:
6
4
2022
pubmed:
1
6
2019
medline:
1
6
2019
Statut:
ppublish
Résumé
The potential value of mesenchymal stromal/stem cell therapy in treating skin fibrosis in scleroderma (systemic sclerosis) and of the caveolin-1 scaffolding domain peptide in treating lung, skin, and heart fibrosis is known. To understand how these observations may relate to differences between mesenchymal stromal/stem cells from healthy subjects and subjects with fibrosis, we have characterized the fibrogenic and adipogenic potential of adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients, from mice with fibrotic lung and skin disease induced by systemic bleomycin treatment, and from healthy controls. Early passage systemic sclerosis adipose-derived mesenchymal stromal/stem cells have a profibrotic/anti-adipogenic phenotype compared to healthy adipose-derived mesenchymal stromal/stem cells (low caveolin-1, high α-smooth muscle actin, high HSP47, low pAKT, low capacity for adipogenic differentiation). This phenotype is mimicked by treating healthy adipose-derived mesenchymal stromal/stem cells with transforming growth factor beta or caveolin-1 small interfering RNA and is reversed in systemic sclerosis adipose-derived mesenchymal stromal/stem cells by treatment with caveolin-1 scaffolding domain peptide, but not scrambled caveolin-1 scaffolding domain peptide. Similar results were obtained with adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients and from bleomycin-treated mice, indicating the central role of caveolin-1 in mesenchymal stromal/stem cell differentiation in fibrotic disease.
Identifiants
pubmed: 35382388
doi: 10.1177/2397198318821510
pii: 10.1177_2397198318821510
pmc: PMC8922642
doi:
Types de publication
Journal Article
Langues
eng
Pagination
127-136Informations de copyright
© The Author(s) 2019.
Déclaration de conflit d'intérêts
Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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