Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis.

ABSTRACT:

Background

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. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.

Methods

The 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.

Results

PVT1 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-?B pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs.

Conclusion

Our study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-?B pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.

SUBMITTER: Zhong W 

PROVIDER: S-EPMC7161221 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature