Abstract
PurposePodocytes 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).MethodsIn 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.ResultsSpironolacton 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 (P < 0.05). Additionally, spironolactone partially blocked the rennin angiotensin aldosterone system (RAAS) by regulating the ACE1, ACE2 and aldosterone levels.ConclusionsIn conclusion, spironolactone promoted autophagy in podocytes and further alleviated DN through partially blocking the RAAS.
Highlights
Diabetic nephropathy (DN) is a devastating microvascular complication of diabetes mellitus (DM)
This study aimed to investigate whether spironolactone could alleviate podocyte loss via promoting autophagy in vivo and examined the underlying molecular mechanism of spironolactone function
Rats in the DN group were randomly divided into DN group (n = 15), DN + IN group treated with 2 units insulin twice a day (n = 15), DN + IN + SP group treated with 2 units insulin twice a day and spironolactone (40 mg/kg, dissolved in 3 mL water) once a day by gavage (n = 15)
Summary
DN is a devastating microvascular complication of diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for up to 40% of end stage renal disease cases [1]. It is characterized by persistent albuminuria, impaired glomerular filtration rate and progressive decline in kidney function [2]. Podocytes are integral for the proper glomerular filtration barrier function. Podocytes are terminally differentiated cells lining the Bowman’s capsule that wrap around the capillaries [3]. Podocyte injury often results in massive proteinuria [4]. Since podocytes do not replicate, the intracellular degradation system is crucial for maintaining their homeostasis
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