Back to Search
Start Over
Calreticulin promotes proliferation and extracellular matrix expression through Notch pathway in cardiac fibroblasts
- Source :
- Advances in Clinical and Experimental Medicine. 27:887-892
- Publication Year :
- 2018
- Publisher :
- Wroclaw Medical University, 2018.
-
Abstract
- BACKGROUND Cardiac fibrosis is one of the most important underlying causes of several cardiac diseases. The role of calreticulin (CRT) in cardiac diseases has already been established. The overor under-expression of CRT can lead to cardiac diseases. OBJECTIVES This study was aimed to explore the effect of CRT on cardiac fibrosis and also to investigate the possible underlying molecular mechanism. MATERIAL AND METHODS Human cardiac fibroblast cells (HCF) were used in the experiment. The cells were transfected with the CRT expression vector constructed by sub-cloning the full-length wild-type CRT coding sequence into pcDNA3.1 (pc-CRT group), empty construct pcDNA3.1 (pcDNA3.1 group), CRT-specific siRNA (si-CRT), and si-NC (negative control). The Cell Counting Kit-8 (CCK-8) assay, apoptosis assay and invasion assay were performed. Quantitative real time polymerase chain reaction (qRT PCR) and western blot analysis were performed to measure the expressions of different mRNAs and proteins. RESULTS The CRT expression was significantly increased (p < 0.01) and decreased (p < 0.01) in the pc-CRT and si-CRT groups, respectively. The CRT over-expression led to increased cell viability and invasiveness (p < 0.05) and a decreased percentage of apoptotic cells. The over-expression of CRT led to a significant increase in the expressions of collagen (I and III) (p < 0.01) and matrix metalloproteinases (MMP-2 and 9) (p < 0.05). The Notch pathway was also significantly activated (p < 0.05) by the over-expression of CRT and vice versa when suppressed. CONCLUSIONS The results showed that the CRT over-expression was associated with increased cell viability and invasiveness and decreased apoptosis, and the activation of the Notch pathway in HCF, which suggests its possible implication in CRT-induced cardiac fibrosis.
- Subjects :
- 0301 basic medicine
genetic structures
Cardiac fibrosis
Notch signaling pathway
Medicine (miscellaneous)
030204 cardiovascular system & hematology
General Biochemistry, Genetics and Molecular Biology
Cell Line
03 medical and health sciences
0302 clinical medicine
Fibrosis
Internal Medicine
medicine
Humans
Pharmacology (medical)
cardiovascular diseases
Viability assay
Genetics (clinical)
Cell Proliferation
Receptors, Notch
biology
Chemistry
Cell growth
Myocardium
Heart
Fibroblasts
equipment and supplies
medicine.disease
Extracellular Matrix
030104 developmental biology
Real-time polymerase chain reaction
Apoptosis
Reviews and References (medical)
cardiovascular system
Cancer research
biology.protein
Calreticulin
Signal Transduction
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 18995276
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Advances in Clinical and Experimental Medicine
- Accession number :
- edsair.doi.dedup.....5051d60812c13fb983db4888f84f6232