Abstract
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. This study was aimed to explore the effect of CRT on cardiac fibrosis and also to investigate the possible underlying molecular mechanism. 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. 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. 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.
Highlights
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 Human cardiac fibroblast cells (HCF), which suggests its possible implication in CRT-induced cardiac fibrosis
Cardiac fibrosis is a pathophysiological condition characterized by the accumulation of extracellular matrix in the myocardium and is considered one of the most important factors implicated in various cardiac diseases.[1,2]
The regenerative capacity of the adult mammalian heart is negligible, and fibrosis occurs in cardiac diseases associated with acute death of cardiomyocytes.[1,2,3,4]
Summary
Cardiac fibrosis is a pathophysiological condition characterized by the accumulation of extracellular matrix in the myocardium and is considered one of the most important factors implicated in various cardiac diseases.[1,2] The regenerative capacity of the adult mammalian heart is negligible, and fibrosis occurs in cardiac diseases associated with acute death of cardiomyocytes.[1,2,3,4] In acute myocardial infarction (AMI), sudden death of a large number of cardiomyocytes leads to the triggering of inflammatory pathways and dead cell replacement with collagen-based scar tissue formation.[5,6] Other than the acute onset of cardiac diseases like AMI, several other chronic cardiac diseases are associated with insidious accumulation of collagen in the interstitial and perivascular regions.[6]. 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 over- or under-expression of CRT can lead to cardiac diseases
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