Microarray analysis reveals long non‑coding RNA SOX2OT as a novel candidate regulator in diabetic nephropathy

Zhang, Xiaoxue; Shang, Jin; Wang, Xiaoyang; Cheng, Genyang; Jiang, Yumin; Liu, Dong; Xiao, Jing; Zhao, Zhanzheng

doi:10.3892/mmr.2018.9534

Cited by 11 publications

(8 citation statements)

References 40 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HG-induced human glomerular mesangial cells (HMCs) was used as in vitro DN experimental model as previously reported [ 21 – 23 ]. We explored the biological function of lncRNA CASC2 and its associated mechanism in DN progression using DN cell model.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling

Dong-ju

Xue

2021

Diabetol Metab Syndr

View full text Add to dashboard Cite

Background Diabetic nephropathy (DN) is a common complication of diabetes. Long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is reported to exert a protective role in DN by a previous study. The working mechanism underlying the protective role of CASC2 in DN progression was further explored in this study. Methods The expression of CASC2 and microRNA-135a-5p (miR-135a-5p) was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability was assessed by Cell Counting Kit-8 (CCK8) assay and 5-ethynyl-29-deoxyuridine (EDU) assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the production of inflammatory cytokines in the supernatant. Western blot assay was performed to analyze protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target relationship between miR-135a-5p and CASC2 or tissue inhibitors of metalloproteinase 3 (TIMP3). Results High glucose (HG) treatment reduced the expression of CASC2 in human glomerular mesangial cells (HMCs) in a time-dependent manner. CASC2 overexpression suppressed HG-induced proliferation, inflammation and fibrosis in HMCs. miR-135a-5p was validated as a target of CASC2, and CASC2 restrained HG-induced influences in HMCs partly by down-regulating miR-135a-5p. miR-135a-5p bound to the 3ʹ untranslated region (3ʹUTR) of TIMP3, and CASC2 positively regulated TIMP3 expression by sponging miR-135a-5p in HMCs. miR-135a-5p silencing inhibited HG-induced effects in HMCs partly by up-regulating its target TIMP3. CASC2 overexpression suppressed HG-induced activation of Jun N-terminal Kinase (JNK) signaling partly through mediating miR-135a-5p/TIMP3 signaling. Conclusions In conclusion, CASC2 alleviated proliferation, inflammation and fibrosis in DN cell model by sponging miR-135a-5p to induce TIMP3 expression.

show abstract

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling

Dong-ju

Xue

2021

Diabetol Metab Syndr

View full text Add to dashboard Cite

show abstract

“…Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in length 7. Recently, various lncRNAs have been studied in the treatment of DN 8–10. lncRNA MEG3 promoted fibrosis and inflammatory response by targeting the miR-181a in vitro and in vivo experiments of DN 11.…”

Section: Introductionmentioning

confidence: 99%

<p>lncRNA GAS5/miR-452-5p Reduces Oxidative Stress and Pyroptosis of High-Glucose-Stimulated Renal Tubular Cells</p>

Xie

Tang

et al. 2019

DMSO

View full text Add to dashboard Cite

BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal failure worldwide. lncRNAs are demonstrated to improve the DN by changing the expression of miRNAs. This study was aimed to investigate the effect of lncRNA GAS5/miR-452-5p on the inflammation, oxidative stress and pyroptosis of high-glucose-induced renal tubular cells.MethodsHK-2 cells were induced by HG to simulate DN cells. RT-qPCR analysis confirmed the transfection effects and detected the expression of GAS5, NLRP3, caspase1, IL-1β, pro-caspase1, pro-IL-1β, GSDMD-N and miR-452-5p. Western blot analysis determined the protein expression of NLRP3, caspase1, IL-1β, pro-caspase1, pro-IL-1β and GSDMD-N. The expression of GSDMD-N was also verified by immunofluorescence. The levels of TNF-α, IL-6, MCP-1, ROS, MDA and SOD were measured by commercial assay kits, respectively. Dual-luciferase reporter assay indicated that GAS5 could combine with miR-452-5p.ResultsGAS5 expression was decreased in HG-induced HK-2 cells. GAS5 overexpression could decrease the levels of TNF-α, IL-6, MCP-1, ROS and MDA and increase the levels of SOD. Moreover, GAS5 overexpression suppressed the expression of NLRP3, caspase1, IL-1β and GSDMD-N, and the results of immunofluorescence verified the above results. miR-452-5p interference could cause the same changes as GAS5 overexpression for HG-induced HK-2 cells, and GAS5 inhibition could reverse the effect of miR-452-5p interference.ConclusionGAS5 overexpression inhibited the inflammation, oxidative stress and pyroptosis of HG-induced renal tubular cells by downregulating the expression of miR-452-5p.

show abstract

“… 48 , 49 Recent studies have reported an association between lncRNAs and the occurrence and development of DN. 50–53 MALAT1, also known as noncoding nuclear-enriched abundant transcript 2 (NET2), is an lncRNA that is widely expressed in human tissues and highly conserved in 33 species of mammals. It has also been reported that MALAT1 plays an important role in DM and its complications.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin Regulates MALAT1/miR-200c/NRF2 Activity to Protect Against Podocyte Pyroptosis Induced by High Glucose

Zuo¹,

Chen²,

He³

et al. 2021

DMSO

View full text Add to dashboard Cite

Background Diabetic nephropathy (DN) is one of the main complications of diabetes mellitus (DM), which leads to the long-term loss of kidney functions. Long noncoding RNAs (LncRNAs) can alleviate DN by interacting with microRNAs (miRNAs). In this work, we aimed to explore the effects of the MALAT1/miR-200c/NRF2 regulatory axis on the pyroptosis and oxidative stress (Oxidative stress, OS) of renal podocytes in high glucose (HG) environment and whether the lipid-lowering drug atorvastatin (AT) can relieve renal OS through this approach. Methods MPC-5, a mouse podocyte cell line, was induced by HG as a cell model. The protein expressions of caspase-1, GSDMD, NLRP3, NRF2, etc. were detected by Western blotting and immunofluorescence, and the mRNA level of caspase-1, GSDMD, NLRP3, NRF2, MALAT1, miR-200c was tested by qRT-PCR. The cell pyroptosis of podocytes treated with AT was verified by CCK-8 or flow cytometry. The levels of Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured by spectrophotometer, respectively. Results The caspase-1 was upregulated in time-dependent manner and got the peak at 48 h and 30 mmol/L respectively in MPC-5 cells treated with HG. Further, the expression of GSDMD, MALAT1 and miR-200c were increased, while the level of NRF2, HO-1, OS-related indicators, were decreased simultaneously. Knockdown the MALAT1 protected MPC-5 cells from pyroptosis and OS induced by HG. However, overexpressing miR-200c in control-group cells increased pyroptosis and upregulated the OS level with HG culture medium. Further, atorvastatin protected MPC-5 cells from cell pyroptosis and downregulated the level of renal OS via attenuating the expression of MALAT1 and miR-200c. Conclusion Atorvastatin protects podocyte cells via MALAT1/miR-200c/NRF2 signal pathway from pyroptosis and OS induced by HG.

show abstract

Microarray analysis reveals long non‑coding RNA SOX2OT as a novel candidate regulator in diabetic nephropathy

Cited by 11 publications

References 40 publications

Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling

Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling

<p>lncRNA GAS5/miR-452-5p Reduces Oxidative Stress and Pyroptosis of High-Glucose-Stimulated Renal Tubular Cells</p>

Atorvastatin Regulates MALAT1/miR-200c/NRF2 Activity to Protect Against Podocyte Pyroptosis Induced by High Glucose

Contact Info

Product

Resources

About