Vascular progenitor cell senescence in patients with Marfan syndrome.
Marfan syndrome
mitochondria dynamics
senescence
transforming growth factor β
vascular progenitor cells
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
02
10
2018
revised:
29
01
2019
accepted:
19
02
2019
pubmed:
29
3
2019
medline:
1
8
2020
entrez:
29
3
2019
Statut:
ppublish
Résumé
Vascular progenitor cells (VPCs) present in the adventitia of the vessel wall play a critical role in the regulation of vascular repair following injury. This study aimed to assess the function of VPCs isolated from patients with Marfan syndrome (MFS). VPCs were isolated from control and MFS donors and characterized. Compared with control-VPCs, MFS-VPCs exhibited cellular senescence as demonstrated by increased cell size, higher SA-β-gal activity and elevated levels of p53 and p21. RNA sequencing showed that several cellular process-related pathways including cell cycle and cellular senescence were significantly enriched in MFP-VPCs. Notably, the expression level of TGF-β1 was much higher in MFS-VPCs than control-VPCs. Treatment of control-VPCs with TGF-β1 significantly enhanced mitochondrial reactive oxidative species (ROS) and induced cellular senescence whereas inhibition of ROS reversed these effects. MFS-VPCs displayed increased mitochondrial fusion and decreased mitochondrial fission. Treatment of control-VPCs with TGF-β1 increased mitochondrial fusion and reduced mitochondrial fission. Nonetheless, treatment of mitofusin2 (Mfn2)-siRNA inhibited TGF-β1-induced mitochondrial fusion and cellular senescence. Furthermore, TGF-β1-induced mitochondrial fusion was mediated by the AMPK signalling pathway. Our study shows that TGF-β1 induces VPC senescence in patients with MFS by mediating mitochondrial dynamics via the AMPK signalling pathway.
Identifiants
pubmed: 30920150
doi: 10.1111/jcmm.14301
pmc: PMC6533473
doi:
Substances chimiques
Reactive Oxygen Species
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4139-4152Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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