Abstract
Podocyte apoptosis importantly contributes to various kidney diseases. Long noncoding RNAs Colon cancer‐associated transcript‐1 (CCAT‐1) has been demonstrated for a critical role in cell proliferation. In the present study, the relationship between CCAT1 and popdocyte impairment, and the underlying mechanism was investigated. Podocytes were isolated from mice and then treated with tumor necrosis factor‐α to simulate podocyte injury. After developed CCAT1 overexpression or knockdown, cell viabilities were determined with the CCK‐8 assay, apoptosis was examined with Flow cytometry, the autophagy was observed by Western blot. Furthermore, phosphorylated PI3K and Akt expressions were examined. We found that after CCAT1 overexpression, the cell viability was significantly increased, apoptosis was significantly decreased, and autophagy was significantly inhibited, which was indicated by induced P62, LC3B‐I and decreased LC3B‐II. In addition, CCAT1 overexpression induced the levels of phosphorylated PI3K and Akt. With Rap treatment, these effects by CCAT1 were reversed. Furthermore, the results contrary to the effects by CCAT1 overexpression were presented after CCAT1 knockdown, and this was inhibited by 3‐MA. Taken together, our results suggested that CCAT1 induction critically participated in apoptosis inhibition in podocytes through autophagy inhibition via increasing PI3K/Akt signaling. This might act as a promising therapeutic intervention for renal diseases associated with podocyte apoptosis.
Highlights
Podocytes are visceral glomerular epithelial cells, lining outside of glomerular basement membrane and forming final glomerular filtration barriers to Yanyan Su and Shuwen Yao contributed to this work.maintain the permeability of the GBM
The inductive and inhibitory effects above mentioned were significantly inhibited after Rap treatment. These indicated that cancer‐associated transcript‐1 (CCAT1) played an important inhibitory role in the autophagy of podocytes induced by Tumor necrosis factor (TNF)‐α, and this effect can be suppressed by Rap
The results indicated that CCAT1 inhibition might significantly increase podocyte autophagy, which might importantly contribute to the cell apoptosis
Summary
Podocytes are visceral glomerular epithelial cells, lining outside of glomerular basement membrane and forming final glomerular filtration barriers to Yanyan Su and Shuwen Yao contributed to this work. Podocyte injury results in marked proteinuria and associated with almost all glomerulopathies, including Focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy, diabetes mellitus (DM), etc.[1]. Autophagy is a critical mode to prevent cell injury.[4,5]. Autophagy is a highly conserved cellular process to maintain intracellular homeostasis by removing impaired protein or damaged organelles, and is essential for the survival of cells. It has been demonstrated that autophagy is renoprotective in many renal diseases, including acute kidney injury, obstructive nephropathy, and diabetic nephropathy.[8]. A few studies have reported that CCAT1 importantly contributes to the regulation of cell apoptosis and autophagy.[13]. We evaluated the role of CCAT1 in the viability of podocytes These results suggest the novel regulatory function of CCAT1 in TNF‐α induced podocyte injury and provide a potential treatment of glomerulosclerosis diseases
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