Sasaki Fuki, Yoshino Hironori, Kusuhara Ayumu, Sato Kota, Tsuruga Eichi
Department of Radiation Science, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan.
Department of Radiological Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan.
Biomed Rep. 2024 Mar 5;20(4):70. doi: 10.3892/br.2024.1758. eCollection 2024 Apr.
In 2012, the threshold radiation dose (0.5 Gy) for cardiovascular and cerebrovascular diseases was revised, and this threshold dose may be exceeded during procedures involving radiation such as interventional radiology. Therefore, in addition to regulating radiation dose, it is necessary to develop strategies to prevent and mitigate the development of cardiovascular disease. Cellular senescence is irreversible arrest of cell proliferation. Although cellular senescence is one of the mechanisms for suppressing cancer, it also has adverse effects. For example, senescence of vascular endothelial cells is involved in development of vascular disorders. However, the mechanisms underlying induction of cellular senescence are not fully understood. Therefore, the present study explored the factors involved in the radiation-induced senescence in human umbilical vein endothelial cells (HUVECs). The present study reanalyzed the gene expression data of senescent normal human endothelial cells and fibroblast after irradiation (NCBI Gene Expression Omnibus accession no. GSE130727) and microarray data of HUVECs 24 h after irradiation (NCBI Gene Expression Omnibus accession no. GSE76484). Numerous genes related to viral infection and inflammation were upregulated in radiation-induced senescent cells. In addition, the gene group involved in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling pathway, which plays an important role to induce anti-viral response, was altered in irradiated HUVECs. Therefore, to investigate the involvement of RIG-I and melanoma differentiation-associated gene 5 (MDA5), which are RLRs, in radiation-induced senescence of HUVECs, the protein expression of RIG-I and MDA5 and the activity of senescence-associated β-galactosidase (SA-β-gal), a representative senescence marker, were analyzed. Of note, knockdown of RIG-I in HUVECs significantly decreased radiation-increased proportion of cells with high SA-β-gal activity (i.e., senescent cells), whereas this phenomenon was not observed in MDA5-knockdown cells. Taken together, the present results suggested that RIG-I, but not MDA5, was associated with radiation-induced senescence in HUVECs.
2012年，心血管和脑血管疾病的阈辐射剂量（0.5 Gy）被修订，在诸如介入放射学等涉及辐射的操作过程中，该阈剂量可能会被超过。因此，除了调节辐射剂量外，有必要制定预防和减轻心血管疾病发生的策略。细胞衰老即细胞增殖的不可逆停滞。虽然细胞衰老作为抑制癌症的机制之一，但它也有不良影响。例如，血管内皮细胞衰老参与血管疾病的发生。然而，诱导细胞衰老的潜在机制尚未完全明确。因此，本研究探讨了人脐静脉内皮细胞（HUVECs）中辐射诱导衰老所涉及的因素。本研究重新分析了辐照后衰老正常人内皮细胞和成纤维细胞的基因表达数据（NCBI基因表达综合数据库登录号：GSE130727）以及辐照后24小时HUVECs的微阵列数据（NCBI基因表达综合数据库登录号：GSE76484）。在辐射诱导的衰老细胞中，许多与病毒感染和炎症相关的基因上调。此外，在辐照的HUVECs中，参与视黄酸诱导基因-I（RIG-I）样受体（RLR）信号通路（在诱导抗病毒反应中起重要作用）的基因组发生了改变。因此，为了研究作为RLRs的RIG-I和黑色素瘤分化相关基因5（MDA5）在HUVECs辐射诱导衰老中的作用，分析了RIG-I和MDA5的蛋白表达以及衰老相关β-半乳糖苷酶（SA-β-gal，一种代表性衰老标志物）的活性。值得注意的是，HUVECs中RIG-I的敲低显著降低了辐射增加的具有高SA-β-gal活性的细胞比例（即衰老细胞），而在MDA5敲低的细胞中未观察到这种现象。综上所述，本研究结果表明，在HUVECs中，与辐射诱导衰老相关的是RIG-I，而非MDA5。
