MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation
MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation
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DOI：
10.1007/s00411-021-00915-9
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发表时间：
2021-05
影响因子：
1.7
通讯作者：
H. Yano;R. Hamanaka;Juan-juan Zhang;M. Yano;M. Hida;Noritaka Matsuo;H. Yoshioka
中科院分区：
文献类型：
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作者：
H. Yano;R. Hamanaka;Juan-juan Zhang;M. Yano;M. Hida;Noritaka Matsuo;H. Yoshioka
放射性纤维化（Radiation-induced fibrosis，RIF）是放射治疗后发生的一种严重并发症，是由胶原等细胞外基质（extracellular matrix，ECM）蛋白沉积引起的。然而，潜在的机制，包括细胞因子的表达，促进RIF过程，尚未完全理解。microRNA（miRNAs）最近被认为是许多基因的转录后抑制因子;然而，它们在RIF过程中的作用仍有待阐明。我们前期的研究表明，电离辐射通过激活转化生长因子（TGF）-β而增加I型胶原的表达，而miR-29抑制了这种增加。本研究旨在探讨电离辐射后，TGF-β下游介质结缔组织生长因子（CTGF）表达受miRNAs转录后调控的机制。电离辐射可增加NIH-3 T3细胞和小鼠胚胎成纤维细胞CTGF的表达。然而，这种增加被TGF-β受体的特异性抑制剂抑制。在可预测的靶向CTGF基因的miRNAs中，miR-26 a的表达在电离辐射暴露后下调，并且这种调节由TGF-β信号负介导。miR-26 a在转录后水平负调控CTGF的表达;然而，电离辐射抑制了这种负调控。此外，miR-26 a的过表达抑制了照射后CTGF和I型胶原的表达。总之，miR-26 a通过TGF-β信号转导调节照射成纤维细胞中CTGF的表达。这些结果提示miR-26 a在RIF治疗中的潜在应用。
Radiation-induced fibrosis (RIF) is a serious complication that occurs after irradiation and which is caused by the deposition of extracellular matrix (ECM) proteins such as collagen. However, the underlying mechanisms, including the expression of the cytokines, that promote the RIF process, are not yet fully understood. MicroRNAs (miRNAs) have recently been suggested to act as post-transcriptional repressors for many genes; however, their role in the process of RIF remains to be elucidated. Our previous study showed that ionizing radiation increased the type I collagen expression through the activation of transforming growth factor (TGF)-β, while miR-29 repressed this increase. This study aimed to investigate the mechanisms by which the expression of connective tissue growth factor (CTGF), a downstream mediator of TGF-β, is controlled by miRNAs post-transcriptionally after exposure to ionizing radiation. The expression of CTGF in NIH-3T3 cells and mouse embryonic fibroblasts was increased by ionizing radiation. However, this increase was suppressed with a specific inhibitor of TGF-β receptor. Among the predictable miRNAs that target the CTGF gene, the expression of miR-26a was downregulated after exposure to ionizing radiation and this regulation was negatively mediated by TGF-β signaling. miR-26a negatively regulated the CTGF expression at the post-transcriptional level; however, ionizing radiation suppressed this negative regulation. In addition, the overexpression of miR-26a inhibited the expression of CTGF and type I collagen after irradiation. In conclusion, miR-26a modulates the expression of CTGF via TGF-β signaling in irradiated fibroblasts. The results suggest the potential application of miR-26a in the treatment of RIF.