Up-regulation of microRNA-93 inhibits TGF-β1-induced EMT and renal fibrogenesis by down-regulation of Orai1

Ma, Jingyun; Zhang, Lei; Hao, Jianbing; Na-qi, LI; Tang, Jie; Hao, Lirong

doi:10.1016/j.jphs.2017.12.010

Cited by 53 publications

(45 citation statements)

References 25 publications

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“…Comparative miR expression profile arrays showed that miR-93 is a signature miR in hyperglycemic condition [24]. Up-regulation of miR-93 inhibits epithelial-mesenchymal transformation and renal fibrogenesis in TGF-β1-induced HK2 cells [25]. Although the biological functions of PTV1 and miR-93 in DN have been mentioned by previous studies, the detailed molecular mechanism of PTV1 involving miR-93 in DN remains unclear.…”

Section: Introductionmentioning

confidence: 94%

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Zhao

Jin

et al. 2020

Bioscience Reports

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Objective: The present study aimed to investigate the regulatory role of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on high glucose (HG)-induced mouse mesangial cells (MMCs). Methods: PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assays were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. The targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 (an online software for analyzing the targeting relationship) and identified by Dual-luciferase reporter (DLR) assay. Results: PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU-positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs. Conclusions: PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

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Section: Introductionmentioning

confidence: 94%

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Zhao

Jin

et al. 2020

Bioscience Reports

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“…Thus, making miR-93 as the potential therapeutic option to alleviate DN. Importantly, miR-93 also negatively regulates the Calcium release-activated calcium channel protein-1 (ORAI1), and reduction of miR-93 expression in DN caused an increase in ORAI1 expression and subsequently promoted TGFB-mediated ECM accumulation and fibrosis (Ma et al, 2018). Excessive ECM accumulation will eventually lead to glomerulosclerosis; therefore, it is the first and crucial step for progressive renal function loss.…”

Section: Micrornas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

et al. 2020

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Diabetic Nephropathy (DN) is the most common cause of End-stage renal disease (ESRD). Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden. Recent findings showed that noncoding RNAs (ncRNAs) play an important role in DN progression, potentially can be used as biomarkers and therapeutic targets. NcRNAs refers to the RNA species that do not encode for any protein, and the most known ncRNAs are the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Dysregulation of these ncRNAs was reported before in DN patients and animal models of DN. Importantly, there are some interactions between these ncRNAs to regulate the crucial steps in DN progression. Here, we aimed to discuss the reported ncRNAs in DN and their interactions with critical genes in DN progression. Elucidating these ncRNAs regulatory network will allow for a better understanding of the molecular mechanisms in DN and how they can act as new biomarkers for DN and also as the potential targets for treatment.

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“…In the present study, in order to simulate renal fibrosis in vitro , the human tubular epithelial cell line HK-2 was treated with TGF-β according to previous reports (19,20). The role of miR-21 in mediating the renal protective effect of quercetin was assessed using TGF-β-induced fibrosis in HK-2 cells to provide a theoretical basis for the treatment of nephropathy using quercetin.…”

Section: Introductionmentioning

confidence: 99%

Quercetin is able to alleviate TGF‑β‑induced fibrosis in renal tubular epithelial cells by suppressing miR‑21

Cao

Jianying

et al. 2018

Exp Ther Med

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Patients with chronic kidney disease (CKD) are characterized by a gradual loss of kidney function over time. A number of studies have indicated that tubule interstitial fibrosis (TIF) is associated with the occurrence and development of CKD. The aim of the present study was to investigate the effect of quercetin treatment on the fibrosis of renal tubular epithelial cells and to determine whether the anti-fibrotic effects of quercetin are achieved via microRNA (miR)-21. Human tubular epithelial HK-2 cells were cultured with transforming growth factor (TGF)-β to induce fibrosis and the expression of fibrotic markers collagen I, fibronectin, α-smooth muscle actin (SMA) and epithelial-cadherin were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cells were treated with 7.5, 15 or 30 mg/ml quercetin, following which fibrosis and miR-21 expression were evaluated. Quercetin-treated cells were transfected with miR-21 mimics and the expression of fibrotic markers was examined using RT-qPCR. Finally, the expression of fibrosis-associated miR-21 target genes, phosphatase and tensin homolog (PTEN) and TIMP Metallopeptidase Inhibitor 3 (TIMP3), was measured in cells treated with quercetin with or without miR-21 mimics using RT-qPCR, western blotting and immunocytochemistry. The results revealed that TGF-β treatment induced a significant increase in the expression of fibrotic markers in HK-2 cells, while quercetin treatment partially inhibited the fibrosis of HK-2 cells. Furthermore, quercetin treatment significantly inhibited TGF-β-induced miR-21 upregulation and transfection with miR-21 mimics reversed the anti-fibrotic effects of quercetin. Quercetin treatment markedly upregulated PTEN and TIMP3 expression, whereas transfection with miR-21 mimics reversed this effect. The results of the present study suggest that quercetin is able to alleviate TGF-β-induced fibrosis in HK-2 cells via suppressing the miR-21 and upregulating PTEN and TIMP3. Quercetin may have potential as an anti-fibrotic treatment for patients with renal fibrosis.

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Up-regulation of microRNA-93 inhibits TGF-β1-induced EMT and renal fibrogenesis by down-regulation of Orai1

Cited by 53 publications

References 25 publications

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

Quercetin is able to alleviate TGF‑β‑induced fibrosis in renal tubular epithelial cells by suppressing miR‑21

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