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Updated: Feb 8, 2026

Author Spotlight: Studying Cardiac Cell-Matrix Interactions In Vitro
Published on: March 22, 2024
Calreticulin promotes proliferation and extracellular matrix expression through Notch pathway in cardiac fibroblasts
Xiaoying Fan1, Yuan Yao1, Yao Zhang1
1Department of Cardiovascular Medicine, 2nd Affiliated Hospital of Harbin Medical University, China.
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.
Insights
Calreticulin (CRT) overexpression in human cardiac fibroblasts increases cell viability and invasiveness, promoting cardiac fibrosis. This suggests CRT plays a key role in cardiac disease development.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Cardiac fibrosis is a major contributor to various heart diseases.
- Calreticulin (CRT) is implicated in cardiac pathologies, with its expression levels affecting disease severity.
Purpose of the Study:
- To investigate the impact of Calreticulin (CRT) on cardiac fibrosis.
- To elucidate the molecular mechanisms underlying CRT's role in cardiac fibrosis.
Main Methods:
- Human cardiac fibroblast cells (HCF) were transfected with CRT expression vectors or siRNA.
- Cell viability, apoptosis, and invasion assays were conducted.
- Gene and protein expression levels were analyzed using qRT-PCR and Western blot.
Main Results:
- CRT overexpression significantly increased HCF viability and invasiveness while decreasing apoptosis.
- CRT overexpression elevated collagen (I and III) and matrix metalloproteinase (MMP-2 and 9) levels.
- The Notch pathway was activated by CRT overexpression and suppressed upon its reduction.
Conclusions:
- CRT overexpression in HCF promotes fibrosis-associated characteristics like increased viability and invasiveness.
- CRT's activation of the Notch pathway is a potential mechanism contributing to CRT-induced cardiac fibrosis.
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