Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Experimental & Molecular Medicine
Dong-Wei LiuZhang-Suo Liu

Abstract

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1...Continue Reading

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Citations

Jul 14, 2020·Journal of Diabetes Research·Jiarong LvShizhong Bu
Aug 6, 2020·Life·Jinwen LinJianghua Chen
Jul 23, 2020·Journal of Diabetes Research·Lili ZhangXiaolin Tong
Oct 30, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Xin He, Xiuya Zeng
Apr 24, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Bing GaoJianping Guo
Aug 3, 2021·Frontiers in Oncology·Pin ZhaoShaojun Xing

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Methods Mentioned

BETA
Assay
PCR
electrophoresis
Co-immunoprecipitation
immunoprecipitation
transfection
RIP
ChIP
flow cytometry

Software Mentioned

lncATLAS
SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis