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Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway
- Source :
- Biochemical and Biophysical Research Communications. 553:172-179
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis. Methods Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFβ1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected. Results After Ang II stimulation, TGFβ1, TGFβ1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFβ1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFβ1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFβ1/MAPK signaling pathway. Conclusions This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFβ1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cell Survival
MAP Kinase Signaling System
Cardiac fibrosis
Biophysics
Dibenzocycloheptenes
Biochemistry
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Rats, Wistar
Protein kinase A
Molecular Biology
Cell Proliferation
biology
Cell growth
Chemistry
Angiotensin II
Myocardium
Cell Differentiation
Cell Biology
Transforming growth factor beta
Fibroblasts
medicine.disease
Fibrosis
Rats
Fibronectin
030104 developmental biology
030220 oncology & carcinogenesis
Schizophrenia
biology.protein
Cancer research
Signal transduction
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 553
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....56ea59b136180cbb6d6a5dcab7e7386b