GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats
GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats
复制标题
GDF15 辐射后通过 MAPK/ERK1/2 通路促进大鼠心脏纤维化和心脏成纤维细胞增殖
DOI：
10.1667/rade-20-00206.1
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发表时间：
2021-08-01
影响因子：
3.4
通讯作者：
Li, Yingdong
中科院分区：
文献类型：
--
作者：
Guo, Huan;Zhao, Xinke;Li, Yingdong
电离辐射暴露与心脏纤维化的风险相关；然而，潜在的分子机制仍不清楚。生长/分化因子 15 (GDF15) 是一种成纤维细胞因子，是转化生长因子 β 超家族的不同成员。下一代测序分析表明，在辐射诱导的纤维化过程中，心脏成纤维细胞中的 Gdf15 增加。然而，Gdf15 在心脏纤维化中的作用仍不清楚。在本研究中，我们证明新生大鼠心脏成纤维细胞和成年大鼠照射后GDF15表达上调可诱导纤维化，体外转染Gdf15后新生大鼠心脏成纤维细胞中细胞增殖率增加和纤维化标志物（Col1α和αSMA）表达增加证实了这一点。相反，GDF15 的下调可抑制心脏纤维化，G2/M 细胞周期停滞、细胞增殖抑制以及 Col1 α 和 α SMA 表达水平低所证实。我们还发现抑制心脏成纤维细胞中Gdf15的表达可能导致CDK1减少并抑制ERK1/2磷酸化。因此，GDF15可能通过MAPK/ERK1/2途径促进心脏成纤维细胞纤维化，从而促进辐射诱发的心脏病的发病机制。 (C) 2021 辐射研究会
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