Chaojie Li, Kan Wang, Jian Fang, Lin Qin, Qiong Ling, Yu Yu
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引用次数: 0
Abstract
This study explored the roles of methionine adenosyltransferase 2A (MAT2A) and tripartite motif containing 25 (TRIM25) in the progression of thoracic aortic aneurysm (TAA). The TAA model was established based on the β-aminopropionitrile method. The effects of MAT2A on thoracic aortic lesions and molecular levels were analyzed by several pathological staining assays (hematoxylin-eosin, Verhoeff-Van Gieson, TUNEL) and molecular biology experiments (qRT-PCR, Western blot). Angiotensin II (Ang-II) was used to induce injury in vascular smooth muscle cells (VSMCs) in vitro. The effects of MAT2A, shMAT2A, shTRIM25 and/or Wnt inhibitor (IWR-1) on the viability, apoptosis and protein expressions of VSMCs were examined by CCK-8, Annexin V-FITC/PI and Western blot assays. In TAA mice, overexpression of MAT2A alleviated thoracic aortic injury, inhibited the aberrant expressions of aortic contractile proteins and dedifferentiation markers, and blocked the activation of Wnt/β-catenin pathway. In Ang-II-induced VSMCs, up-regulation of MAT2A increased cellular activity and repressed the expression of β-catenin protein. TRIM25 knockdown promoted activity of VSMCs, inhibited apoptosis, and blocked the Wnt/β-catenin pathway activation by binding to MAT2A. IWR-1 partially counteracted the regulatory effects of shMAT2A. Collectively, TRIM25 destabilises the mRNA of MAT2A to activate Wnt/β-catenin signaling and ultimately exacerbate TAA injury.
期刊介绍:
Human Molecular Genetics concentrates on full-length research papers covering a wide range of topics in all aspects of human molecular genetics. These include:
the molecular basis of human genetic disease
developmental genetics
cancer genetics
neurogenetics
chromosome and genome structure and function
therapy of genetic disease
stem cells in human genetic disease and therapy, including the application of iPS cells
genome-wide association studies
mouse and other models of human diseases
functional genomics
computational genomics
In addition, the journal also publishes research on other model systems for the analysis of genes, especially when there is an obvious relevance to human genetics.