Radiation-induced premature cellular senescence involved in glomerular diseases in rats.
Radiation-induced premature cellular senescence involved in glomerular diseases in rats.
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DOI：
10.1038/s41598-018-34893-8
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发表时间：
2018-11-14
影响因子：
4.6
通讯作者：
Tsuruoka S
中科院分区：
文献类型：
--
作者：
Aratani S;Tagawa M;Nagasaka S;Sakai Y;Shimizu A;Tsuruoka S
目前，细胞衰老已成为慢性器官疾病的一个基本因素。辐射是诱导细胞衰老的应激因素之一。虽然肾脏被认为是一个对辐射敏感的器官，但辐射诱导的细胞衰老是否以及如何与肾脏疾病相关仍不清楚。在这项研究中，我们对7-8周龄的雄性大鼠进行了实验，这些大鼠在单侧肾脏接受了单剂量的18-戈伊辐射。受照射的肾脏显示出细胞衰老的标志，包括SA-β-gal活性增加、细胞周期蛋白依赖性激酶抑制剂（p53、p21和p16）上调以及DNA增殖标记物（Ki-67）缺失。此外，结合体外实验，我们证明，辐射诱导的衰老肾小球内皮细胞获得改变的基因表达，即衰老相关的分泌表型（特别是，IL-6），这可能是由NF-κ B信号通路触发。病理学分析提示严重的肾小球内皮细胞损伤，表现为血栓性微血管病、肾小球塌陷和内皮细胞数量减少。我们认为，肾小球内皮细胞更容易受到辐射诱导的细胞衰老。总之，目前的研究是第一个确定的重要作用，辐射诱导的细胞衰老，主要来自肾小球内皮细胞，肾小球损伤的发展。
Currently, cellular senescence has emerged as a fundamental contributor to chronic organ diseases. Radiation is one of the stress factors that induce cellular senescence. Although the kidney is known as a radiosensitive organ, whether and how radiation-induced cellular senescence is associated with kidney diseases remains unclear. In this study, we performed experiments on 7–8-week-old male rats that received a single dose of 18-Gy radiation in the unilateral kidney. The irradiated kidneys showed hallmarks of cellular senescence, including increased SA-β-gal activity, upregulation of cyclin-dependent kinase inhibitor (p53, p21, and p16), and absence of DNA proliferation marker (Ki-67). Furthermore, combined with in-vitro experiments, we demonstrated that radiation-induced senescent glomerular endothelial cells acquired altered gene expression, namely, senescence-associated secretory phenotype (particularly, IL-6), which might be triggered by NF-kB signaling pathway. Pathological analysis suggested severe glomerular endothelial cell injury, as evidenced by thrombotic microangiopathy, collapsing glomeruli, and reduced endothelial cell numbers. We suggested that glomerular endothelial cells were more susceptible to radiation-induced cellular senescence. In conclusion, the current study is the first to identify the important role of radiation-induced cellular senescence, mainly derived from glomerular endothelial cells, for the development of glomerular injury.
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影响因子：
3
作者：
Kitada K;Nakano D;Ohsaki H;Hitomi H;Minamino T;Yatabe J;Felder RA;Mori H;Masaki T;Kobori H;Nishiyama A
通讯作者：
Nishiyama A
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
6
作者：
Mannava, Sudha;Moparthy, Kalyana C.;Nikiforov, Mikhail A.
通讯作者：
Nikiforov, Mikhail A.
影响因子：
7.8
作者：
Liu, Jun;Yang, Ju-Rong;Xiao, Hua-Shi
通讯作者：
Xiao, Hua-Shi