Vascular progenitor cell senescence in patients with Marfan syndrome.
Haiwei HeBaoqi YuZipeng LiuGen YeWei YouYimei HongQizhou LianYuelin ZhangXin LiPublished in: Journal of cellular and molecular medicine (2019)
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.
Keyphrases
- oxidative stress
- dna damage
- transforming growth factor
- endothelial cells
- cell cycle
- diabetic rats
- high glucose
- stress induced
- cell death
- single cell
- cell proliferation
- stem cells
- skeletal muscle
- poor prognosis
- case report
- epithelial mesenchymal transition
- drug induced
- mesenchymal stem cells
- long non coding rna
- replacement therapy