Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli
| Autor: | Jianghu Zhao, Lihui Gao, Xiangwei Xu, Xiao-Dan Wang, Ling Li, Zhenkun Li, Jingling Song, Hua Lin, Jinwen Wang, Yumin Yin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Xanthones Kidney Glomerulus AMP-Activated Protein Kinases Podocyte End stage renal disease Nephropathy Diabetic nephropathy Nephrin Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound medicine Autophagy Animals Autophagy-Related Protein-1 Homolog Diabetic Nephropathies Mangiferin PI3K/AKT/mTOR pathway Pharmacology biology business.industry Podocytes TOR Serine-Threonine Kinases medicine.disease Rats 030104 developmental biology medicine.anatomical_structure chemistry Cytoprotection Cancer research biology.protein Disease Progression business |
| Zdroj: | European journal of pharmacology. 824 |
| ISSN: | 1879-0712 |
| Popis: | Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN. In the present study, we investigated the effects of mangiferin on nephropathy in streptozotocin (STZ)-induced diabetic rats; we focused on pathological factors related to autophagy in podocytes and the AMPK-mTOR-ULK1 pathway. The results showed that chronic treatment with mangiferin significantly decreased albuminuria, inhibited glomerular extracellular matrix expansion and restored the expression of nephrin, a podocyte marker, in diabetic rats; these results suggest that mangiferin delayed the process of DN and protected the podocytes. In addition, mangiferin induced autophagy, as shown by the up-regulation of LC3 II and the down-regulation of p62 in both DN rats and podocytes. Transmission electron microscope analyses showed that mangiferin increased the number of autophagosomes in the podocytes of DN rats. This underlying mechanism was associated with the up-regulation of AMPK phosphorylation, the down-regulation of mTOR phosphorylation and the up-regulation of p-ULK1. Taken together, mangiferin delayed the progression of DN and protected the podocytes by enhancing autophagy under diabetic conditions via the AMPK-mTOR-ULK1 pathway. These findings provide new insights into the molecular mechanisms underlying the renoprotective effects of mangiferin in DN. |
| Databáze: | OpenAIRE |
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