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Nur77 deficiency exacerbates cardiac fibrosis after myocardial infarction by promoting endothelial‐to‐mesenchymal transition
- Source :
- Journal of Cellular Physiology. 236:495-506
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Cardiac fibrosis is a reparative process after myocardial infarction (MI), which leads to cardiac remodeling and finally heart failure. Endothelial-to-mesenchymal transition (EndMT) is induced after MI and contributes to cardiac fibrosis after MI. Orphan nuclear receptor Nur77 is a key regulator of inflammation, angiogenesis, proliferation, and apoptosis in vascular endothelial cells. Here, we investigated the role of orphan nuclear receptor Nur77 in EndMT and cardiac fibrosis after MI. Cardiac fibrosis was induced through MI by ligation of the left anterior descending coronary artery. We demonstrated that Nur77 knockout aggravated cardiac dysfunction and cardiac fibrosis 30 days after MI. Moreover, Nur77 deficiency resulted in enhanced EndMT as shown by increased expression of FSP-1, SM22α, Snail, and decreased expression of PECAM-1 and eNOS compared with wild-type mice after MI. Then, we found overexpression Nur77 in human coronary artery endothelial cells significantly inhibited interleukin 1β and transforming growth factor β2-induced EndMT, as shown by a reduced transition to a fibroblast-like phenotype and preserved angiogenesis potential. Mechanistically, we demonstrated that Nur77 downregulated EndMT by inhibiting the nuclear factor-κB-dependent pathway. In conclusion, Nur77 is involved in cardiac fibrosis by inhibiting EndMT and may be a promising target for therapy of cardiac fibrosis after MI.
- Subjects :
- Male
0301 basic medicine
Epithelial-Mesenchymal Transition
Nerve growth factor IB
Physiology
Angiogenesis
Cardiac fibrosis
Interleukin-1beta
Clinical Biochemistry
Myocardial Infarction
Inflammation
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Enos
Nuclear Receptor Subfamily 4, Group A, Member 1
medicine
Animals
Humans
Endothelium
Myocardial infarction
Cells, Cultured
Mice, Knockout
Neovascularization, Pathologic
biology
business.industry
Myocardium
NF-kappa B
Endothelial Cells
Heart
Cell Biology
biology.organism_classification
medicine.disease
Coronary Vessels
Fibrosis
Mice, Inbred C57BL
030104 developmental biology
030220 oncology & carcinogenesis
Heart failure
cardiovascular system
Cancer research
medicine.symptom
business
Signal Transduction
Transforming growth factor
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 236
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....747b8de2173fe8825824d70def337b64