Abstract
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.
Highlights
At present, the pathophysiology of IgA nephropathy(IgAN) still remains unclear and may be related to many factors, such as infections, immune responses, inflammatory mediators, genetics, etc. [1,2]
Rapamycin was kindly provided by Hangzhou East China Pharmaceutical Co; rabbit AKT polyclonal antibody was bought from CST company (Cat no:9272S); rabbit p70S6K polyclonal antibody was bought from Fitzgerald company (Cat no:70R-36369); rabbit GAPDH monoclonal antibody was bought from CST company(Cat no:2118S)
IgA nephropathy is the most frequent form of primary glomerulonephritis that occurs in China and worldwide, and it is one of the most important causes of end-stage renal failure [10]
Summary
The pathophysiology of IgA nephropathy(IgAN) still remains unclear and may be related to many factors, such as infections, immune responses, inflammatory mediators, genetics, etc. [1,2]. Many studies suggested that the abnormal glycosylation of IgA molecules and the formation of immune complexes played important roles in the pathogenesis of IgAN [3]. We speculate that rapamycin may play an important role in the prevention and treatment of IgA nephropathy through its anti-inflammatory and anti-proliferative effects. 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. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. Conclusion: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. The result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway
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