Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression

作者：Gong, Bin; Wang, Zhiwei^*; Zhang, Min; Hu, Zhipeng; Ren, Zongli; Tang, Zheng; Jiang, Wanli; Cheng, Lianghao; Huang, Jun; Ren, Wei; Wang, Qingtao

来源：Annals of Vascular Surgery, 2017, 40: 243-251.

DOI：10.1016/j.avsg.2016.07.091

• INTERNATIONAL REGISTRY
• MEDIAL DEGENERATION
• MDM2
• P53
• PROTEIN
• EXPRESSION
• ANEURYSM
• DISEASE
• CELLS
• GENE

Background: The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 (murine double minute 2) feedback loop in the formation of TAD, and one of a potential feedback loop regulator, TRIM25 (tripartite motif protein-25).
Methods: Surgical specimens of the aorta from TAD patients (n = 10) and controls (n = 10) were tested for alpha-smooth muscle actin (alpha-SMA), p53, MDM2, and TRIM25 by western blot, immunohistochemical staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively.
Results: When compared with controls, western blot shows that the protein levels of p53, MDM2, and TRIM25 were increased significantly in the aortic media of TAD patients. qRT-PCR further verified that the mRNA expression of MDM2 and TRIM25 was also increased 6- and 4-folds, respectively, in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of alpha-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD.
Conclusion: This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression.

• 出版日期2017-4
• 单位武汉大学