Three TF Co-expression Modules Regulate Pressure-Overload Cardiac Hypertrophy in Male Mice
| Autor: | Yu-Wang Chang, Chien-Chang Chen, Li Ling, Ya-Ting Chang, Wen-Hsiung Li, Yao-Ming Chang, Arthur Chun-Chieh Shih |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Time Factors Science Cardiomegaly 030204 cardiovascular system & hematology Biology Bioinformatics Article Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Gene expression microRNA medicine Animals Longitudinal Studies RNA Messenger Gene Transcription factor Aorta Pressure overload Multidisciplinary Gene Expression Profiling medicine.disease Cell biology Gene expression profiling 030104 developmental biology Heart failure Hypertension Medicine Transcription Factors |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-07981-4 |
| Popis: | Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes. |
| Databáze: | OpenAIRE |
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