Runt‐related transcription factor 1 (Runx1) aggravates pathological cardiac hypertrophy by promoting p53 expression
| Autor: | Cui Liang, Pengcheng Li, Chenran Guo, Dianhong Zhang, Lulu Yang, Binbin Du, Zheng-Yang Hao, Lingyao Kong, Yanzhou Zhang, Xiaoxu Tian, Jian-Zeng Dong |
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| Rok vydání: | 2021 |
| Předmět: |
p53
DNA damage heart failure Cardiomegaly Stimulation Mice chemistry.chemical_compound Mediator Runx1 hemic and lymphatic diseases medicine Animals Myocytes Cardiac Transcription factor Cells Cultured Pressure overload Mice Inbred BALB C Gene knockdown business.industry cardiac hypertrophy Original Articles Cell Biology medicine.disease Rats Disease Models Animal Gene Expression Regulation RUNX1 chemistry Gene Knockdown Techniques Heart failure Core Binding Factor Alpha 2 Subunit embryonic structures cardiovascular system Cancer research Molecular Medicine Original Article Tumor Suppressor Protein p53 business Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Cardiac hypertrophy and the resultant heart failure are among the most common causes of morbidity and mortality worldwide; thus, identifying the key factor mediating pathological cardiac hypertrophy is critically important for developing the strategy to protect against heart failure. Runx1 (Runt‐related transcription factor 1) acts as an essential transcription factor that functions in a variety of cellular processes including differentiation, proliferation, tissue growth and DNA damage response. However, relatively little is known about the role of Runx1 in heart, especially cardiac hypertrophy and heart failure. In the present study, we investigated the role of Runx1 in experimentally pathological cardiac hypertrophy. The in vitro model was induced by Ang II exposure to cultured neonatal rat cardiomyocytes, and the in vivo pathological cardiac hypertrophy models were induced by chronic pressure overload in mice. Runx1 expression is increased in heart tissues from mice with pressure overload–induced cardiac hypertrophy and in neonatal rat cardiomyocytes in response to Ang II stimulation. Moreover, knockdown of cardiac Runx1 alleviates the pressure overload–induced cardiac hypertrophy. Mechanistically, Runx1 activates the p53 signalling by binding to the p53 gene and promotes its transcription. Rescue experiments indicate that Runx1 promotes cardiac hypertrophy in a p53‐dependent manner. Remarkably, we demonstrated that Ro5‐3335 (a Runx1 inhibitor) acts as a potential therapeutic drug for treating pathological cardiac hypertrophy. In summary, we conclude that Runx1 is a novel mediator and therapeutic target for pathological cardiac hypertrophy. |
| Databáze: | OpenAIRE |
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