Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316 This issue Cite

Research Paper

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

Yucai Chen1, Tianyi Yuan1,2, Huifang Zhang1, Yu Yan1, Danshu Wang1, Lianhua Fang1✉, Yang Lu3, Guanhua Du2✉

1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines;
2. Beijing Key Laboratory of Drug Targets Identification and Drug Screening;
3. Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

✉ Corresponding authors: Professor Lianhua Fang and Professor Guanhua Du, National center for pharmaceutical screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nan Wei Road, Beijing 100050, More

Citation:
Chen Y, Yuan T, Zhang H, Yan Y, Wang D, Fang L, Lu Y, Du G. Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316. https://www.ijbs.com/v13p1067.htm
Other styles

File import instruction

Abstract

Graphic abstract

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.

Keywords: salvianolic acid A, endothelial-to-mesenchymal transition, TGFβ1, Nrf2, pulmonary arterial hypertension, antioxidant

Citation styles

APA
Chen, Y., Yuan, T., Zhang, H., Yan, Y., Wang, D., Fang, L., Lu, Y., Du, G. (2017). Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. International Journal of Biological Sciences, 13(8), 1067-1081. https://doi.org/10.7150/ijbs.20316.

ACS
Chen, Y.; Yuan, T.; Zhang, H.; Yan, Y.; Wang, D.; Fang, L.; Lu, Y.; Du, G. Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. Int. J. Biol. Sci. 2017, 13 (8), 1067-1081. DOI: 10.7150/ijbs.20316.

NLM
Chen Y, Yuan T, Zhang H, Yan Y, Wang D, Fang L, Lu Y, Du G. Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316. https://www.ijbs.com/v13p1067.htm

CSE
Chen Y, Yuan T, Zhang H, Yan Y, Wang D, Fang L, Lu Y, Du G. 2017. Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. Int J Biol Sci. 13(8):1067-1081.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use