Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1/Notch1.
Humans
Mesenchymal Stem Cells
/ metabolism
Extracellular Vesicles
/ metabolism
Skin Aging
/ radiation effects
Tissue Inhibitor of Metalloproteinase-1
/ genetics
Receptor, Notch1
/ genetics
Umbilical Cord
/ cytology
Adipose Tissue
/ metabolism
Ultraviolet Rays
/ adverse effects
Mice
DNA Damage
Animals
Reactive Oxygen Species
/ metabolism
Keratinocytes
/ metabolism
Journal
Signal transduction and targeted therapy
ISSN: 2059-3635
Titre abrégé: Signal Transduct Target Ther
Pays: England
ID NLM: 101676423
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
23
04
2024
accepted:
26
09
2024
revised:
13
09
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.
Identifiants
pubmed: 39472581
doi: 10.1038/s41392-024-01993-z
pii: 10.1038/s41392-024-01993-z
doi:
Substances chimiques
Tissue Inhibitor of Metalloproteinase-1
0
Receptor, Notch1
0
NOTCH1 protein, human
0
TIMP1 protein, human
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
294Informations de copyright
© 2024. The Author(s).
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