Abstract
Glomerular diseases are commonly characterized by podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine podocyte recovery. It was shown that trehalose induced podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human podocytes and showed cytoprotective effects in PAN-treated podocytes.
Highlights
Glomerular diseases are characterized by the disrupted renal filtration barrier which consists of endothelial cells, basement membrane and epithelial cells
Trehalose induced autophagy in human podocytes To test whether trehalose induces autophagy in human podocytes, we investigated the expression of LC3 and Atg5 in treated cells
Podocyte damage is regarded as the determining factor of glomerular diseases [31]
Summary
Glomerular diseases are characterized by the disrupted renal filtration barrier which consists of endothelial cells, basement membrane and epithelial cells ( called podocytes). The ideal therapeutic strategies of glomerular diseases are aiming to ameliorate podocyte injury including apoptosis and actin cytoskeleton rearrangement. Autophagy has emerged as a potential approach recently It is a highly conserved catabolic mechanism of which the unwanted organelles and misfolded proteins are delivered to lysosome for degradation [6]. Autophagy deficient mice present with accumulated dysfunction proteins, endoplasmic reticulum stress and proteinuria. They are more susceptible to drug-induced models of glomerular diseases [8]. It is suggested that autophagy may be harnessed for the treatment of glomerular diseases, as it may attenuate podocyte injury by eliminating harmful stimuli [6,11]
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