Limits...
Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis

View Article: PubMed Central - PubMed

ABSTRACT

Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity.

No MeSH data available.


Related in: MedlinePlus

A schematic diagram revealing the underlying mechanisms of As2O3 induced EndMT and cardiac fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037371&req=5

f8: A schematic diagram revealing the underlying mechanisms of As2O3 induced EndMT and cardiac fibrosis.

Mentions: In the present study, we made an effort to understand the potential role of EndMT in As2O3-induced cardiac fibrosis. First, in vivo study showed that EndMT was present in the progression of cardiac fibrosis and cardiac dysfunction. Second, in vitro study confirmed that As2O3 could result in EndMT in HAECs, and this process was partly mediated by the AKT/GSK-3β/Snail pathway. The proposed mechanism is illustrated in Fig. 8.


Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis
A schematic diagram revealing the underlying mechanisms of As2O3 induced EndMT and cardiac fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037371&req=5

f8: A schematic diagram revealing the underlying mechanisms of As2O3 induced EndMT and cardiac fibrosis.
Mentions: In the present study, we made an effort to understand the potential role of EndMT in As2O3-induced cardiac fibrosis. First, in vivo study showed that EndMT was present in the progression of cardiac fibrosis and cardiac dysfunction. Second, in vitro study confirmed that As2O3 could result in EndMT in HAECs, and this process was partly mediated by the AKT/GSK-3β/Snail pathway. The proposed mechanism is illustrated in Fig. 8.

View Article: PubMed Central - PubMed

ABSTRACT

Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity.

No MeSH data available.


Related in: MedlinePlus