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. 2017:2017:6147294.
doi: 10.1155/2017/6147294. Epub 2017 Mar 27.

Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

Affiliations

Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

Shian Huang et al. Biomed Res Int. 2017.

Abstract

This study aimed to investigate the effects and mechanisms of quercetin on pulmonary arterial endothelial cell (PAEC) transdifferentiation into smooth muscle-like cells. TGF-β1-induced PAEC transdifferentiation models were applied to evaluate the pharmacological actions of quercetin. PAEC proliferation was detected with CCK8 method and BurdU immunocytochemistry. Meanwhile, the identification and transdifferentiation of PAECs were determined by FVIII immunofluorescence staining and α-SMA protein expression. The related mechanism was elucidated based on the levels of Akt and Erk1/2 signal pathways. As a result, quercetin effectively inhibited the TGF-β1-induced proliferation and transdifferentiation of the PAECs and activation of Akt/Erk1/2 cascade in the cells. In conclusion, quercetin is demonstrated to be effective for pulmonary arterial hypertension (PAH) probably by inhibiting endothelial transdifferentiation possibly via modulating Akt and Erk1/2 expressions.

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Figures

Figure 1
Figure 1
Effect of quercetin on PAEC viability was evaluated by CCK-8 assay (n = 4 per group). P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group.
Figure 2
Figure 2
Effect of quercetin on PAEC proliferation by BrdU methods. (a) BrdU immunocytochemistry (scale bar = 100 μm); (b) cell count with BrdU staining, P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group.
Figure 3
Figure 3
Transdifferentiation of endothelial cells in the cells expressing α-SMA induced by TGF-β1, as detected by cell immunofluorescence. (a)(A) Blank control PAECs (4x); (a)(B) identification of human PAECs by immunofluorescence. Red staining represents FVIII (10x); (a)(C) blank control PAECs (10x); (a)(D) TGF-β1-induced PAECs. Green staining represents α-SMA (10x); (a)(E) TGF-β1 + quercetin-treated PAECs (10x); (b) conversion rate of PAECs in different groups (n = 4 per group), P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group.
Figure 4
Figure 4
α-SMA protein expression in transdifferentiation of endothelial cells. (a) Western blot assay; (b) comparison of gray values of western blot (n = 4 per group), P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group.
Figure 5
Figure 5
Expression and phosphorylation levels of Akt and Erk1/2 in PAECs in different treatment groups. (a1) Western blot assay of Akt protein; (a2) comparison of gray values of western blot assay of Akt protein (n = 4 per group), P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group; (b1) western blot assay of Erk1/2 protein; (b2) comparison of gray values of western blot assay of Erk1/2 protein (n = 4 per group), P < 0.05, the control group versus the TGF-β1-induced group and the TGF-β1-induced group versus the TGF-β1 + quercetin-treated group.

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