The protective effect and mechanism of rapamycin in the rat model of IgA nephropathy
The protective effect and mechanism of rapamycin in the rat model of IgA nephropathy
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DOI：
10.1080/0886022x.2019.1577257
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发表时间：
2019-01-01
期刊：
影响因子：
3
通讯作者：
Tian, Jun
中科院分区：
文献类型：
--
作者：
Guo, Ning;Liu, Shengli;Tian, Jun
背景：IgA肾病的发病机制迄今尚不清楚。目前，有研究揭示mTOR通路可能参与IgA肾病的发生；然而，其机制尚未得到系统研究。在本研究中，我们建立了IgAN大鼠模型，以研究雷帕霉素作为一种新型免疫抑制剂的保护作用及其治疗机制。方法：建立IgA肾病模型后，给予大鼠不同浓度雷帕霉素治疗，观察不同浓度雷帕霉素对大鼠肾功能的保护作用。通过免疫荧光观察IgA的沉积。雷帕霉素处理后，采用蛋白质印迹法检测肾脏 mTOR 通路中 Akt 和 p70S6k 蛋白的表达。结果：形态学和免疫荧光证实IgA肾病大鼠模型建立成功。特别是，蛋白尿水平随着雷帕霉素剂量的增加以及肾小球中IgA沉积的增加而降低。此外，Western blot分析表明，大鼠模型中mTOR通路下游p70S6K表达下降，mTOR通路上游蛋白AKT过表达。结论：我们发现雷帕霉素对IgA肾病大鼠模型具有剂量依赖性的保护作用。此外，Western blot检测结果提示雷帕霉素可能通过干扰AKT-mTOR-p70S6K信号通路发挥治疗作用。
Background: The pathogenesis of the development of IgA nephropathy has not been clear up to now. At present, some studies revealed that the mTOR pathway may participate in IgA nephropathy; however, the mechanism has not been systematically studied. In this study, we established an IgAN rat model to investigate the protective effects of rapamycin as a new type of immunosuppressant, as well as its therapeutic mechanisms. Methods: After the establishment of IgA nephropathy model, rats were treated with different concentrations of rapamycin, and the protective effect of different concentrations of rapamycin on renal function of the rats was observed. The deposition of IgA was observed by immunofluorescence. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. Results: Morphology and immunofluorescence confirmed that the rat model of IgA nephropathy was successfully established. In particular, the level of proteinuria decreased with the increase of the dose of rapamycin, as well as the deposition of IgA in glomeruli. Moreover, the western blot analysis indicated that the expression of p70S6K in the downstream of mTOR pathway decreased and the upstream protein AKT of the mTOR pathway was overexpressed in the rats model. Conclusion: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. In addition, the result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway.