Li Diangeng, Zhao Delong, Zhang Weiguang, Ma Qian, Liu Dong, Huang Qi, Zheng Ying, Bai Xueyuan, Sun Xuefeng, Chen Xiangmei
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing 100853, China.
Aging (Albany NY). 2018 Jun 14;10(6):1192-1205. doi: 10.18632/aging.101460.
We established a young (Y)-old (O) rat kidney transplantation model. With this model, we detected no age-related differences in renal structure between Y→Y and Y→O kidneys or O→O and O→Y kidneys. However, we did detect differences in levels of the senescence markers β-gal and p16 as well as the inflammatory cytokines TNF-α and IL-1β. Using proteomics analysis we detected 66 proteins associated with suppression of aging and 73 proteins associated with enhancement of aging. After construction of a protein-protein interaction network, a total of 73 nodes and 99 edges were analyzed using MCODE, and three significant modules were selected. GO and KEGG analyses showed that these proteins were mainly located in mitochondria and were largely related to oxidative stress. Among them, SOD1 expression was lower in Y→O than Y→Y kidneys and higher in O→Y than O→O kidneys. Acetylated (Ac)-NF-κB showed the opposite expression profile. In addition, SOD1 expression was higher in primary tubular epithelial cells from young rats than old rats, and SOD1 knockdown led to increased Ac-NF-κB expression. These findings suggest the local renal environment, particularly oxidative stress/mitochondrial function, affects renal aging.
我们建立了年轻（Y）-老年（O）大鼠肾脏移植模型。利用该模型，我们未检测到Y→Y和Y→O肾脏之间或O→O和O→Y肾脏之间在肾脏结构上存在与年龄相关的差异。然而，我们确实检测到衰老标志物β-半乳糖苷酶和p16以及炎性细胞因子肿瘤坏死因子-α和白细胞介素-1β水平存在差异。通过蛋白质组学分析，我们检测到66种与衰老抑制相关的蛋白质和73种与衰老增强相关的蛋白质。构建蛋白质-蛋白质相互作用网络后，使用MCODE分析了总共73个节点和99条边，并选择了三个重要模块。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，这些蛋白质主要位于线粒体中，并且在很大程度上与氧化应激相关。其中，超氧化物歧化酶1（SOD1）在Y→O肾脏中的表达低于Y→Y肾脏，在O→Y肾脏中的表达高于O→O肾脏。乙酰化（Ac）-核因子-κB呈现相反的表达模式。此外，年轻大鼠原代肾小管上皮细胞中SOD1的表达高于老年大鼠，并且SOD1基因敲低导致Ac-NF-κB表达增加。这些发现表明局部肾脏环境，特别是氧化应激/线粒体功能，影响肾脏衰老。
