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Int Urol Nephrol. 2019 Apr;51(4):755-764. doi: 10.1007/s11255-019-02074-9. Epub 2019 Feb 8.

Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes.

Author information

1
Department of Nephrology, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
2
Basic Medical Science, Jilin University, Changchun, Jilin, People's Republic of China.
3
Department of Nephrology, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China. singer_zh@sina.com.

Abstract

PURPOSE:

Podocytes are terminally differentiated cells lining the Bowman's capsule. Podocytes are critical for the proper glomerular filtration barrier function. At the same time, autophagy is crucial for maintaining podocyte homeostasis and insufficient autophagy could cause podocyte loss and proteinuria that is commonly observed in diabetic nephropathy (DN).

METHODS:

In this study, we investigated the role of spironolactone in podocyte loss and autophagy. DN model was established in male Sprague-Dawley rats using high-fat diet and low-dose streptozotocin. The impact of spironolactone on metabolic and biochemical parameters were tested by automatic biochemical analyzer. The angiotensin converting enzyme 1 and 2 (ACE1 and ACE2) and aldosterone were examined by ELISA. We examined the kidney histology and autophagy in podocytes by histochemical staining and electron microscopy. Podocyte loss and autophagy were analyzed by anti-NPHS2 and anti-WT1 as well as anti-Beclin1 and anti-LC3B, respectively.

RESULTS:

Spironolacton decreased the urinary albumin excretion, lipids and fasting glucose levels, and alleviated kidney damage. Further, spironolactone increased the expression of the podocyte-specific markers WT1 and NPHS2, as well as the autophagic markers Beclin1 and LC3B (Pā€‰<ā€‰0.05). Additionally, spironolactone partially blocked the rennin angiotensin aldosterone system (RAAS) by regulating the ACE1, ACE2 and aldosterone levels.

CONCLUSIONS:

In conclusion, spironolactone promoted autophagy in podocytes and further alleviated DN through partially blocking the RAAS.

KEYWORDS:

Autophagy; Diabetic nephropathy; Podocytes; Rennin angiotensin aldosterone system; Spironolactone

PMID:
30734886
DOI:
10.1007/s11255-019-02074-9

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