Hepatocyte senescence induced by radiation and partial hepatectomy in rat liver
Hepatocyte senescence induced by radiation and partial hepatectomy in rat liver
复制标题
DOI：
10.3109/09553002.2014.922714
复制
发表时间：
2014-05
影响因子：
2.6
通讯作者：
M. Serra;F. Marongiu;M. Sini;Michela Marongiu;A. Contini;H. Wolff;M. Rave-Frank;P. Krause;E. Laconi;S. Koenig
中科院分区：
文献类型：
--
作者：
M. Serra;F. Marongiu;M. Sini;Michela Marongiu;A. Contini;H. Wolff;M. Rave-Frank;P. Krause;E. Laconi;S. Koenig
摘要目的：暴露于辐射引发的肝脏广泛取代居民实质细胞移植肝细胞。这种重新种群形成的机制仍有待澄清。在这些研究中，我们检查了在体内细胞衰老的可能发生辐射相关的预处理的宿主肝脏。材料和方法：Fischer 344大鼠接受外照射，计算机断层扫描为基础的部分肝脏照射。25戈伊的单次剂量被输送到右肝叶（肝脏质量的40%）。另一组动物在照射后4天接受1/3部分肝切除术（切除左前叶）。非辐照组作为对照。所有大鼠在初始处理后四周处死。结果如下：照射的肝脏显示出几种细胞衰老的标志物，包括衰老相关β-半乳糖苷酶（SA-β-gal）的表达、细胞大小的增加以及细胞周期蛋白依赖性激酶抑制剂（CDK-I）p16和p21的上调。此外，定量逆转录聚合酶链反应（qRT-PCR）分析显示衰老相关分泌表型（SASP）的激活，包括细胞因子白细胞介素6（IL 6）和1α（IL 1 α）。衰老相关的变化在接受部分肝切除术（PH）后照射（IR）的大鼠中更为突出。结论：我们的结论是，启动与辐射肝再生的结果在诱导细胞衰老和上调衰老相关的分泌表型。后者可以促进移植细胞在该系统中的广泛生长。
Abstract Purpose: Exposure to radiation primes the liver for extensive replacement of the resident parenchymal cells by transplanted hepatocytes. The mechanisms underlying this repopulation remain to be clarified. In these studies, we examined the possible occurrence of cell senescence in vivo following radiation-associated preconditioning of the host liver. Materials and methods: Fischer 344 rats underwent external-beam, computed-tomography-based partial liver irradiation. A single dose of 25 Gy was delivered to the right liver lobes (40% of liver mass). An additional group of animals received a 1/3 partial hepatectomy (removal of the left anterior lobe) four days after irradiation. Non-irradiated groups served as controls. All rats were sacrificed four weeks after the initial treatment. Results: The irradiated livers displayed several markers of cell senescence, including expression of senescence-associated-β-galactosidase (SA-β-gal), increase in cell size, and up-regulation of cyclin-dependent kinase inhibitors (CDK-I) p16 and p21. Furthermore, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed activation of the senescence-associated secretory phenotype (SASP), including the cytokines interleukin 6 (IL6) and 1α (IL1α). The senescence-related changes were more prominent in rats undergoing partial hepatectomy (PH) following irradiation (IR). Conclusions: We conclude that priming with radiation for liver repopulation results in the induction of cell senescence and the up-regulation of a senescence-associated secretory phenotype. The latter can contribute to the extensive growth of transplanted cells in this system.