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Epigenetics and expression of key genes associated with cardiac fibrosis: NLRP3, MMP2, MMP9, CCN2/CTGF and AGT

AIMS: Excessive inflammatory signaling and pathological remodeling of the extracellular matrix drive cardiac fibrosis and require changes in gene expression. MATERIALS AND METHODS: Using bioinformatics, both tissue-specific expression profiles and epigenomic profiles of some genes critical for cardi...

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Detalles Bibliográficos
Autores principales: Chandra, Sruti, Ehrlich, Kenneth C, Lacey, Michelle, Baribault, Carl, Ehrlich, Melanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Future Medicine Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907962/
https://www.ncbi.nlm.nih.gov/pubmed/33538177
http://dx.doi.org/10.2217/epi-2020-0446
Descripción
Sumario:AIMS: Excessive inflammatory signaling and pathological remodeling of the extracellular matrix drive cardiac fibrosis and require changes in gene expression. MATERIALS AND METHODS: Using bioinformatics, both tissue-specific expression profiles and epigenomic profiles of some genes critical for cardiac fibrosis were examined, namely, NLRP3, MMP2, MMP9, CCN2/CTGF, AGT (encodes angiotensin II precursors) and hsa-mir-223 (post-transcriptionally regulates NLRP3). RESULTS: In monocytes, neutrophils, fibroblasts, venous cells, liver and brain, enhancers or super-enhancers were found that correlate with high expression of these genes. One enhancer extended into a silent gene neighbor. These enhancers harbored tissue-specific foci of DNA hypomethylation, open chromatin and transcription factor binding. CONCLUSIONS: This study identified previously undescribed enhancers containing hypomethylated transcription factor binding subregions that are predicted to regulate expression of these cardiac fibrosis-inducing genes.