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  • Podocyte autophagic activity plays a protective role in renal injury and delays the progression of podocytopathies.

Podocyte autophagic activity plays a protective role in renal injury and delays the progression of podocytopathies.

The Journal of pathology (2014-05-30)
Caihong Zeng, Yun Fan, Junnan Wu, Shaolin Shi, Zhaohong Chen, Yongzhong Zhong, Changming Zhang, Ke Zen, Zhihong Liu
ABSTRACT

The progression of podocytopathies is quite variable among patients and the underlying reason for this remains unclear. Here, we report that autophagic activity in podocytes plays a critical role in controlling the progression of podocytopathies. Morphological and biochemical studies on renal biopsies from patients with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) showed that glomeruli, and in particular podocytes, from MCD patients had higher levels of Beclin1-mediated autophagic activity than glomeruli from FSGS patients. Repeat renal biopsies of MCD patients enabled tracking of podocyte autophagic activity and confirmed that patients maintaining high podocyte autophagic activity retained MCD status, whereas patients with decreased podocyte autophagic activity progressed to FSGS. Inhibition of autophagic activity, by knocking down Beclin1 or by treating with 3-methyladenine (3-MA) or chloroquine, enhanced puromycin aminonucleoside (PAN)-induced apoptosis of podocytes. In contrast, rapamycin-mediated promotion of autophagic activity decreased this apoptosis. In PAN-treated rats, inhibition of autophagy with 3-MA or chloroquine resulted in earlier onset and greater proteinuria, more extensive foot-process effacement, and reduction in podocyte markers, whereas rapamycin-mediated stimulation of autophagy led to decreased proteinuria and less severe foot-process effacement, but higher expression of podocyte markers. This study demonstrates that podocyte autophagic activity plays a critical protective role in renal injury and that maintaining podocyte autophagic activity represents a potential therapeutic strategy for controlling the progression of podocytopathies.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SYNPO antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Supelco
Rapamycin, VETRANAL®, analytical standard
Sigma-Aldrich
Rapamycin from Streptomyces hygroscopicus, ≥95% (HPLC), powder
Sigma-Aldrich
Puromycin aminonucleoside
Sigma-Aldrich
Rapamycin, Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM), from Streptomyces hygroscopicus
Sigma-Aldrich
Anti-LC3B antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
3-Methyladenine, autophagy inhibitor
Sigma-Aldrich
Anti-Podocin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution