Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice
Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice
复制标题
衰老加速小鼠中衰老相关的肾损伤和炎症与 Klotho 的下调和 RIG-I/NF-κB 信号通路的诱导有关
DOI：
10.1007/s40520-015-0371-y
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发表时间：
2016-02-01
影响因子：
4
通讯作者：
Du, Jun-Rong
中科院分区：
文献类型：
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作者：
Zeng, Yi;Wang, Ping-Han;Du, Jun-Rong
抗衰老 Klotho 蛋白在肾脏和大脑中的主要分布可能表明其在衰老过程中防止肾-脑轴功能障碍方面发挥着重要作用。我们之前的研究表明，Klotho 的下调与衰老加速小鼠 pron-8 (SAMP8) 小鼠的衰老相关认知障碍有关。本研究调查了 Klotho 在衰老相关炎症和肾损伤中的潜在作用。使用年龄和性别匹配的 SAMP8 小鼠组及其相应的正常对照衰老加速小鼠抵抗-1 (SAMR1)来研究 Klotho 在衰老相关炎症和肾损伤中的潜在作用。与老年 SAMR1 对照相比，早期慢性肾病 (CKD)（与尿白蛋白与肌酐比值增加有关）、炎症在老年 SAMP8 小鼠中观察到细胞浸润、肾小球硬化和肾小管间质纤维化。此外，与 SAMR1 对照相比，Klotho 诱导的视黄酸诱导基因 1/核因子 kappa B (RIG-I/NF-kappa B) 信号通路的激活丧失，以及随后在老年 SAMP8 小鼠肾脏中产生促炎介质肿瘤坏死因子 α、白细胞介素 6 和诱导型一氧化氮合酶。目前的结果表明，衰老相关的炎症和早期 CKD 可能与 12 个月大的 SAMP8 小鼠中 Klotho 的下调和 RIG-I/NF-kappa B 信号通路的诱导有关。此外，具有认知缺陷和肾损伤的老年SAMP8小鼠可能是研究衰老过程中肾脑轴的潜在小鼠模型。
The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury.Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury.Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-kappa B (RIG-I/NF-kappa B) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor alpha, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls.The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-kappa B signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.