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Rapamycin prevents early steps of the development of diabetic nephropathy in rats
Yi Yang1, Jingjing Wang, Ling Qin
1Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Background/Aims:
Recent studies suggested the involvement of the Akt/mammalian target of rapamycin (mTOR) pathway in the pathogenesis of diabetic nephropathy. The effect of mTOR blockade by rapamycin in diabetic nephropathy was investigated, but in vivo study of rapamycin treatment in the course of early diabetes is still insufficient. This study was designed to determine the therapeutic effects of rapamycin on diabetic nephropathy at an early stage.
Methods:
Diabetes was induced in Sprague-Dawley rats with streptozotocin, and rapamycin (1 mg/kg) was administered by daily gavage for 4 weeks. Renal structural changes and some factors involved in the early pathogenesis of diabetic nephropathy were tested. The activation level of the Akt/mTOR pathway was also determined.
Results:
Rapamycin treatment reduced albuminuria, glomerular enlargement, glomerular basement membrane thickening, renal macrophage recruitment, and levels of renal mRNA expression of proliferating cell nuclear antigen, transforming growth factor-beta1, vascular endothelial growth factor, and monocyte chemoattractant protein-1 without change in blood glucose level and blood pressure in experimental diabetic rats. In addition, treatment with rapamycin also down-regulated the enhanced levels of renal p-Akt, phospho-p70S6 kinase, and phospho-ribosomal S6 protein in diabetic rats.
Conclusions:
Rapamycin treatment can prevent the early renal structural changes of diabetes in experimental rats, and thus halt the early steps of the development of diabetic nephropathy. mTOR blockade might be beneficial for the treatment of diabetic nephropathy.
Insights
Rapamycin treatment prevents early diabetic nephropathy in rats by blocking the Akt/mammalian target of rapamycin (mTOR) pathway. This intervention reduces kidney damage without affecting blood glucose or pressure.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- The Akt/mammalian target of rapamycin (mTOR) pathway is implicated in diabetic nephropathy.
- Limited in vivo studies exist on early-stage diabetic nephropathy treatment with rapamycin.
Purpose of the Study:
- To investigate the therapeutic effects of rapamycin on early-stage diabetic nephropathy.
- To evaluate the impact of mTOR blockade on diabetic kidney disease progression.
Main Methods:
- Diabetes induced in Sprague-Dawley rats using streptozotocin.
- Daily oral administration of rapamycin (1 mg/kg) for 4 weeks.
- Assessment of renal structural changes and Akt/mTOR pathway activation.
Main Results:
- Rapamycin reduced albuminuria, glomerular hypertrophy, and basement membrane thickening.
- Decreased renal macrophage infiltration and expression of key pathogenic factors (PCNA, TGF-β1, VEGF, MCP-1).
- Down-regulation of phosphorylated Akt, p70S6K, and S6 ribosomal protein in kidneys.
Conclusions:
- Rapamycin prevents early renal structural damage in experimental diabetic rats.
- mTOR blockade shows potential as a therapeutic strategy for diabetic nephropathy.
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