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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Paeonol Attenuates the Endothelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Umbilical Vein Endothelial Cells through ALK5- Smad2/3 Signaling Pathway

Author(s): Yulong Yang, Yuning Liang, Xiaoyan Shi, Hongfei Wu, Yarong Liu, Tingting Jiang, Jinjin Yan, Min Zhou, Menglong Gao and Min Dai*

Volume 20, Issue 1, 2023

Published on: 22 February, 2023

Page: [76 - 84] Pages: 9

DOI: 10.2174/1567202620666230202124037

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Paeonol (Pae), the main active compound of the root of Paeonia albiflora, is efficacious in treating atherosclerosis (AS). Endothelial dysfunction is throughout the pathological progression of AS. It is expected that inhibition of Endothelial-to-mesenchymal transition (EndMT) will be a key target for AS treatment.

Objective: In this study, we investigated the molecular mechanism of the regulatory effect of Pae on EndMT in human umbilical vein endothelial cells (HUVECs).

Methods: Cell cytotoxicity, proliferation, and migration were detected by CCK-8, the wound healing assay, and EdU staining, respectively. The protein expressions were measured by Western blot or immunofluorescence staining. Immunofluorescence staining was performed to indicate endothelial cells undergoing EndMT in ApoE-/- mice. In vitro TGF-β1-induced EndMT assays were performed in HUVECs and the effect of Pae was explored.

Results: We demonstrated that Pae could improve induced TGF-β1-EndMT in vivo and in vitro. Mechanism study revealed that Pae directly bonds to the activin-like kinase 5 (ALK5, also known as TGFβ type I receptor), inhibited downstream Smad2/3 phosphorylation, and thus alleviated EndMT. Notably, overexpression of ALK5 significantly reversed the inhibitory effect of Pae on EndMT in HUVECs.

Conclusion: Our results indicate that ALK5 is a promising druggable target for AS, and pharmacological regulation of ALK5-Smad2/3 signaling pathway with small-molecule holds great potential to benefit AS patients.

Keywords: Paeonol, atherosclerosis, endothelial-to-mesenchymal transition, activin receptor-like kinase 5, human umbilical vein endothelial cells, transforming growth factor-β1.

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