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Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways
Shian Huang1,2,3, Xiulong Zhu4, Wenjun Huang5
1Cardiovascular Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
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.
Insights
Quercetin effectively inhibits pulmonary arterial endothelial cell transdifferentiation, a key process in pulmonary arterial hypertension. This suggests quercetin may be a potential therapeutic agent for PAH by modulating cell signaling pathways.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pharmacology
Background:
- Pulmonary arterial hypertension (PAH) involves pulmonary arterial endothelial cell (PAEC) dysfunction.
- Endothelial-to-smooth muscle-like cell transdifferentiation is a critical mechanism in PAH pathogenesis.
- Targeting endothelial cell behavior offers a potential therapeutic strategy for PAH.
Purpose of the Study:
- To investigate the effects of quercetin on PAEC transdifferentiation.
- To elucidate the underlying molecular mechanisms of quercetin's action.
- To evaluate quercetin's potential therapeutic role in PAH.
Main Methods:
- Utilized transforming growth factor-beta 1 (TGF-β1)-induced PAEC transdifferentiation models.
- Assessed PAEC proliferation using CCK8 assay and BrdU immunocytochemistry.
- Determined PAEC identification and transdifferentiation via FVIII immunofluorescence and alpha-smooth muscle actin (α-SMA) expression.
- Analyzed the involvement of Akt and Erk1/2 signaling pathways.
Main Results:
- Quercetin significantly inhibited TGF-β1-induced PAEC proliferation and transdifferentiation.
- Quercetin suppressed the activation of the Akt and Erk1/2 signaling cascades in PAECs.
- FVIII expression decreased while α-SMA expression increased, indicating reduced endothelial markers and increased smooth muscle markers.
Conclusions:
- Quercetin demonstrates efficacy in preventing PAEC transdifferentiation.
- Quercetin may exert its therapeutic effects in PAH by inhibiting endothelial-to-smooth muscle-like cell transition.
- Modulation of Akt and Erk1/2 pathways is a likely mechanism for quercetin's action in PAH.