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CREG ameliorates the phenotypic switching of cardiac fibroblasts after myocardial infarction via modulation of CDC42
- Source :
- Cell Death and Disease, Vol 12, Iss 4, Pp 1-16 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Phenotype switching of cardiac fibroblasts into myofibroblasts plays important role in cardiac fibrosis following myocardial infarction (MI). Cellular repressor of E1A-stimulated genes (CREG) protects against vascular and cardiac remodeling induced by angiotensin-II. However, the effects and mechanisms of CREG on phenotype switching of cardiac fibroblasts after MI are unknown. This study aimed to investigate the role of CREG on the phenotype switching of cardiac fibroblasts following MI and its mechanism. Our findings demonstrated that, compared with littermate control mice, cardiac function was deteriorated in CREG+/− mice on day 14 post-MI. Fibrosis size, αSMA, and collagen-1 expressions were increased in the border regions of CREG+/− mice on day 14 post-MI. Conversely, exogenous CREG protein significantly improved cardiac function, inhibited fibrosis, and reduced the expressions of αSMA and collagen-1 in the border regions of C57BL/6J mice on day 14. In vitro, CREG recombinant protein inhibited αSMA and collagen-1 expression and blocked the hypoxia-induced proliferation and migration of cardiac fibroblasts, which was mediated through the inhibition of cell division control protein 42 (CDC42) expression. Our findings could help in establishing new strategies based on the clarification of the role of the key molecule CREG in phenotype switching of cardiac fibroblasts following MI.
- Subjects :
- Cardiac function curve
Male
Cancer Research
Cardiac fibrosis
Immunology
Phenotypic switching
Myocardial Infarction
Heart failure
CDC42
Article
Cellular and Molecular Neuroscience
Fibrosis
medicine
Animals
Myocardial infarction
lcsh:QH573-671
Myofibroblasts
cdc42 GTP-Binding Protein
Cells, Cultured
business.industry
lcsh:Cytology
Myocardium
Cell Biology
Fibroblasts
medicine.disease
Phenotype
Cell biology
Mice, Inbred C57BL
Repressor Proteins
Disease Models, Animal
Mechanisms of disease
business
Myofibroblast
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....ed96e3e990534825170dc38a4c2add28