Abstract
BackgroundDiabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.MethodsThe expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was performed to determine protein expression. Cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS) assay. The targeted correlation between miR-23b-3p and PVT1 or WT1 was verified by dual-luciferase reporter assay.ResultsPVT1 and WT1 were highly expressed in the serum of DN patients and high glucose (HG)-induced mesangial cells (MCs). The knockdown of PVT1 or WT1 ameliorated HG-induced proliferation and fibrosis in MCs. Mechanistically, PVT1 modulated WT1 expression through acting as a molecular sponge of miR-23b-3p. The miR-23b-3p/WT1 axis mediated the protective effect of PVT1 knockdown on HG-induced proliferation and fibrosis in MCs. The NF-κB pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs.ConclusionOur study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-κB pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.
Highlights
Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2
plasmacytoma variant translocation 1 (PVT1) expression was elevated in HGinduced human mesangial cells (MCs), and its depletion weakened the expression of several extracellular matrix (ECM) proteins, eliciting a crucial involvement of PVT1 in DN pathogenesis [12]
Our study suggested that PVT1 knockdown alleviated HGinduced proliferation and fibrosis in human MCs possibly through targeting the miR-23b-3p/Wilms tumor protein 1 (WT1)/nuclear factor-κB (NF-κB) pathway
Summary
Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. We aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis. Plasmacytoma variant translocation 1 (PVT1), a 1.9 kb long lncRNA, has been found as a potential locus for diabetic end-stage kidney disease (ESRD) by a pooling-based genome polymorphism study [10]. PVT1 expression was elevated in HGinduced human MCs, and its depletion weakened the expression of several ECM proteins, eliciting a crucial involvement of PVT1 in DN pathogenesis [12]. We aimed was to further explore the effect and underlying mechanism of PVT1 on HGinduced MCs proliferation and fibrosis
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