Abstract
Long non-coding RNAs (lncRNAs) are important regulators in diabetic nephropathy. In this study, we investigated the potential role of lncRNA TUG1 in regulating endoplasmic reticulum stress (ERS)-mediated apoptosis in high glucose induced renal tubular epithelial cells. Human renal tubular epithelial cell line HK-2 was challenged with high glucose following transfection with lncRNA TUG1, miR-29c-3p mimics or inhibitor expression plasmid, either alone or in combination, for different experimental purposes. Potential binding effects between TUG1 and miR-29c-3p, as well as between miR-29c-3p and SIRT1 were verified. High glucose induced apoptosis and ERS in HK-2 cells, and significantly decreased TUG1 expression. Overexpressed TUG1 could prevent high glucose-induced apoptosis and alleviated ERS via negatively regulating miR-29c-3p. In contrast, miR-29c-3p increased HK-2 cells apoptosis and ERS upon high glucose-challenge. SIRT1 was a direct target gene of miR-29c-3p in HK-2 cells, which participated in the effects of miR-29c-3p on HK-2 cells. Mechanistically, TUG1 suppressed the expression of miR-29c-3p, thus counteracting its function in downregulating the level of SIRT1. TUG1 regulates miR-29c-3p/SIRT1 and subsequent ERS to relieve high glucose induced renal epithelial cells injury, and suggests a potential role for TUG1 as a promising diagnostic marker of diabetic nephropathy.
Highlights
Diabetic nephropathy is one of the most common complications of diabetes and is the major triggering factor for kidney failure
The results showed that high glucose induced apparent HK-2 cell apoptosis in a dose-dependent manner as assessed by flow cytometry (Fig 1A)
We found that the levels of Caspase12, Glucoseregulated protein 78 kDa (GRP78), C/EBP homologous protein (CHOP) were observably increased by high glucose stimulation (Fig 1C)
Summary
Diabetic nephropathy is one of the most common complications of diabetes and is the major triggering factor for kidney failure. Typical symptoms of diabetic nephropathy include blood pressure dysregulation, loss of appetite, nausea and vomiting, persistent itching and fatigue, causing great physical and mental suffering to diabetic nephropathy patients[1, 2]. Diabetic nephropathy patients often have a high risk of mortality, mostly caused by cardiovascular complications[3]. TUG1/miR-29c-3p/SIRT1 regulates ERS in diabetic nephropathy in vitro
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