BioOne.org will be down briefly for maintenance on 17 December 2024 between 18:00-22:00 Pacific Time US. We apologize for any inconvenience.
How to translate text using browser tools
21 May 2021 GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats
Huan Guo, Xinke Zhao, Haining Li, Kedan Liu, Hugang Jiang, Xiangting Zeng, Juan Chang, Chengxu Ma, Zhaoyuan Fu, Xinfang Lv, Tao Wang, Hongyun Guo, Kai Liu, Haixiang Su, Yingdong Li
Author Affiliations +
Abstract

Ionizing radiation exposure is associated with a risk of cardiac fibrosis; however, the underlying molecular mechanism remains unclear. Growth/differentiation factor-15 (GDF15), a fibroblast factor, is a divergent member of the transforming growth factor β superfamily. Next-generation sequencing analyses has revealed that Gdf15 is increased in cardiac fibroblasts during radiation-induced fibrosis. However, the role of Gdf15 in cardiac fibrosis remains unclear. In this study, we demonstrated that the upregulated expression of GDF15 in newborn rat cardiac fibroblasts and adult rats after irradiation could induce fibrosis, which was confirmed by the increased cell proliferation rate and the increased expression of fibrosis markers (Col1α and αSMA) in newborn rat cardiac fibroblasts after transfection with Gdf15 in vitro. Conversely, the downregulation of GDF15 inhibited cardiac fibrosis, as confirmed by G2/M-cell cycle arrest, suppression of cell proliferation, and low levels of Col1α and αSMA expression. We also found that suppressing the expression of Gdf15 in cardiac fibroblasts could lead to a decrease in CDK1 and inhibit phosphorylation of ERK1/2. Thus, GDF15 might promote cardiac fibroblast fibrosis through the MAPK/ERK1/2 pathway and thus contribute to the pathogenesis of radiation-induced heart disease.

©2021 by Radiation Research Society. All rights of reproduction in any form reserved.
Huan Guo, Xinke Zhao, Haining Li, Kedan Liu, Hugang Jiang, Xiangting Zeng, Juan Chang, Chengxu Ma, Zhaoyuan Fu, Xinfang Lv, Tao Wang, Hongyun Guo, Kai Liu, Haixiang Su, and Yingdong Li "GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats," Radiation Research 196(2), 183-191, (21 May 2021). https://doi.org/10.1667/RADE-20-00206.1
Received: 26 August 2020; Accepted: 22 April 2021; Published: 21 May 2021
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top