Background: Modern lifestyle changes and the interlinking of non-communicable diseases result in the development of chronic kidney disease (CKD). While research has focused on attenuating the CKD, the role of mTOR in the progression of CKD is still unclear. Objectives: The current investigation was undertaken to study the role of mTOR-mediated signaling in CKD using Wistar male rats and adenine-induced CKD as an experimental model. Method: The animals were divided into 3 groups, representing control, CKD, and rapamycin-pretreated rats. At the end of the experimental period, blood biochemical indexes on kidney function and expression levels of fibrotic markers, including TGF-β, PAI-1, α-smooth muscle action, fibronectin, CTGF, and collagen-1, were analyzed. In addition, kidney injury markers such as kim-1, cystatin-C, NAG, and NGAL, indicating a progressive fibrotic response, were also studied. Results: The results suggest that mTOR inhibition significantly attenuated the induction of fibrosis, with restored serum creatinine and blood urea nitrogen levels. Intriguingly, the microRNA (miRNA) analysis revealed an increased expression of miR-193–5p, miR-221, miR-212, and miR-183–5p in CKD, while an increased mRNA expression of anti-inflammatory cytokines and reduced level of pS6K with attenuated miRNA was found in rapamycin-treated rats compared to the CKD animals. Conclusion: Activation of mTOR is the major responsive element with activation of miRNAs as an elementary role in the progression of kidney disease. Hence, targeting mTOR would be a possible strategy of treatment for CKD.
Neuroimmunomodulation

中文翻译：

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mTOR信号的减弱是大鼠慢性肾脏病抢救途径中的主要反应因素。

背景：现代生活方式的改变和非传染性疾病的相互联系导致了慢性肾脏病（CKD）的发展。尽管研究集中在减弱CKD上，但mTOR在CKD进展中的作用仍不清楚。目的：以Wistar雄性大鼠和腺嘌呤诱导的CKD为实验模型，进行了当前的研究以研究mTOR介导的信号在CKD中的作用。方法：将动物分为3组，分别代表对照，CKD和雷帕霉素预处理的大鼠。在实验期结束时，分析了血液生化指标对肾功能和纤维化标志物表达水平的影响，包括TGF-β，PAI-1，α-平滑肌作用，纤连蛋白，CTGF和胶原蛋白-1。此外，还研究了肾脏损伤标记物，如kim-1，胱抑素C，NAG和NGAL，它们表明了进行性纤维化反应。结果：结果表明，mTOR抑制显着减弱了纤维化的诱导，恢复了血清肌酐和血液尿素氮水平。有趣的是，microRNA（miRNA）分析显示CKD中miR-193-5p，miR-221，miR-212和miR-183-5p的表达增加，而抗炎细胞因子的mRNA表达增加，而CKD的水平降低。与CKD动物相比，在雷帕霉素治疗的大鼠中发现了带有减弱的miRNA的pS6K。结论： mTOR的激活是主要的响应元件，miRNA的激活是肾脏疾病进展的基本作用。因此，靶向mTOR将是CKD治疗的可能策略。
神经免疫调节