LINC00462 is involved in high glucose-induced apoptosis of renal tubular epithelial cells via AKT pathway.

Abstract

New evidences suggest that long non-coding RNAs (lncRNAs) may play important roles in a variety of kidney diseases, including diabetic nephropathy (DN). Our present study investigated the potential function of LINC00462 in high glucose (HG)-induced apoptosis of renal tubular epithelial cells (RTEC) and to determine the underlying mechanism. The expression of LINC00462 in renal biopsy tissues was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, a loss of function assay was performed to determine the protective effect of LINC00462 in HG-induced RTEC damage. In addition, the downstream signaling pathway of LINC00462 was also investigated. The qRT-PCR results showed that the expression of LINC00462 was significantly up-regulated in renal biopsies from DN patients. At the same time, LINC00462 was enhanced in a glucose concentration- and time-dependent manner in human kidney (HK-2 and HKC) cells subjected to HG treatment. The knockdown of LINC00462 improved the significantly reduced cell viability of HG treatment, decreased HG-induced reactive oxygen species (ROS) and malondialdehyde levels, and up-regulated the response of antioxidant systems to ROS by increasing superoxide dismutase and catalase levels. In addition, knockdown of LINC00462 inhibited HG-induced cell apoptosis and affected the expression of apoptosis-related proteins. Most importantly, we found that knockdown of LINC00462 enhanced the expression of p-AKT. Moreover, AKT-specific inhibitor LY294002 restored the effect of LINC00462 knockdown on apoptosis. In conclusion, our study demonstrated that knockdown of LINC00462 can ameliorate oxidative stress and apoptosis in HG-induced RTEC by activating the AKT pathway, suggesting that knockdown of LINC00462 may provide a potential therapeutic approach for DN.