Abstract
BackgroundLong non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. However, the role of lncRNA HOX transcript antisense RNA (HOTAIR) in diabetic nephropathy (DN) remains unclear.MethodsHigh glucose (HG)-induced human mesangial cells (HMC) was used to construct DN cell models in vitro. HMC proliferation was evaluated by CCK8 assay and EDU staining. Protein levels of proliferation markers, fibrosis markers, and wingless-type family member 2B (WNT2B) were measured using western blot analysis. HMC oxidative stress was assessed by determining the levels of oxygen species and malondialdehyde, as well as superoxide dismutase activity. Relative expression levels of lncRNA HOTAIR, microRNA (miR)-147a, and WNT2B were examined using quantitative real-time PCR. The interaction between miR-147a and lncRNA HOTAIR or WNT2B was confirmed by dual-luciferase reporter assay and RIP assay.ResultsOur data showed that lncRNA HOTAIR knockdown could inhibit the proliferation, fibrosis, and oxidative stress in HG-induced HMC. LncRNA HOTAIR could serve as a sponge of miR-147a. The inhibition effect of lncRNA HOTAIR silencing on the biological functions of HG-induced HMC could be reversed by miR-147a inhibitor. WNT2B was targeted by miR-147a, and its overexpression also overturned the suppressive effect of miR-147a on the proliferation, fibrosis, and oxidative stress of HG-induced HMC.ConclusionIn total, our research pointed out that lncRNA HOTAIR could mediate miR-147a/WNT2B axis to promote DN progression.
Highlights
Long non-coding RNAs have been shown to be involved in the regulation of many disease progression
high glucose (HG) induced human mesangial cells (HMC) proliferation, fibrosis and oxidative stress To determine whether HG-induced diabetic nephropathy (DN) cell model in vitro was successful, we evaluated the proliferation, fibrosis, and oxidative stress capacity of HMC
After the transfected HMC was treated with HG, we discovered that the suppressive effect of Long non-coding RNAs (lncRNAs) HOX transcript antisense RNA (HOTAIR) knockdown on HMC viability and the percentage of EDU positive cells could be reversed by miR-147a inhibitor (Fig. 4C, E)
Summary
Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. Long noncoding RNA (lncRNA) is a type of RNA transcript that does not encode protein, and its abnormal expression has been confirmed to be related to human diseases progression [7, 8]. LncRNA GAS5 was confirmed to hinder mesangial cell proliferation and fibrosis through the miR-221/SIRT1 axis, so it might play a negative role in DN progression [12]. High expression of lncRNA KCNQ1OT1 in DN could accelerate HGinduced HMC proliferation, oxidative stress and extracellular matrix (ECM) deposition, promoting the development of DN [13]. All these evidences make us believe that lncRNAs are an important participants in DN development
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