title: Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression.
abstract: 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 α-smooth muscle actin (α-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 α-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. Electronic address: wangzhiwp@126.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Lianghao
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D016022:Case-Control Studies; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D000070584:Tripartite Motif Proteins / Q000032:analysis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D044767:Ubiquitin-Protein Ligases / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D012333:RNA, Messenger; C495901:TP53 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases