文献类型：期刊文献

英文题名：GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats

作者：Guo, Huan[1,2,3];Zhao, Xinke[4,5];Li, Haining[3];Liu, Kedan[3];Jiang, Hugang[1];Zeng, Xiangting[6];Chang, Juan[1];Ma, Chengxu[7];Fu, Zhaoyuan[1];Lv, Xinfang[1];Wang, Tao[3];Guo, Hongyun[3];Liu, Kai[1,4];Su, Haixiang[3];Li, Yingdong[1,2]

第一作者：Guo, Huan;郭华

通信作者：Li, YD[1];Liu, K[2];Li, YD[2];Su, HX[3]

机构：[1]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China;[2]Lan Zhou Univ, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China;[3]Gansu Prov Canc Hosp, Gansu Prov Acad Inst Med Sci, Lanzhou, Gansu, Peoples R China;[4]Affiliated Hosp Gansu Univ Chinese Med, Dept Intervent Sect, Lanzhou, Gansu, Peoples R China;[5]Fu Wai Hosp, Chinese Acad Med Sci, Beijing, Peoples R China;[6]Lan Zhou Univ, Hosp 2, Lanzhou, Gansu, Peoples R China;[7]Lanzhou Univ, Dept Endocrinol, Hosp 1, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), 199 Dong Gang West Rd, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), 2 Xiaoxihu East St, Lanzhou 730050, Gansu, Peoples R China.

年份：2021

卷号：196

期号：2

起止页码：183

外文期刊名：RADIATION RESEARCH

收录：;Scopus(收录号：2-s2.0-85111594174);WOS:【SCI-EXPANDED(收录号:WOS:000679659900005)】；

基金：This work was supported by the National Natural Science Foundation of China (grant nos. 81760798, 81873132 and 81860786).

语种：英文

摘要：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 beta 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 (Col1 alpha and alpha SMA) 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 Col1 alpha and alpha SMA 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. (C) 2021 by Radiation Research Society