The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy

Zhang, Yajuan; Sun, Yan; Peng, Rui; Liu, Handeng; He, Weihao; Zhang, Luyu; Peng, Huimin; Zhang, Zheng

doi:10.1159/000495590

Cited by 24 publications

(15 citation statements)

References 48 publications

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“…LncRNAs can effectively participate in the pathophysiological process of DN 29,30 . For instance, we found that lncRNA 150Rik can promote proliferation of mesangial cells via regulating miR‐451 and p38 MAPK pathway in DN 31 . LncRNA MEG3 enhances fibrosis and inflammatory response through modulating miR‐181a, Egr‐1 and TLR4 axis in DN 32 …”

Section: Discussionmentioning

confidence: 90%

Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression

et al. 2020

J Cellular Molecular Medi

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Diabetic nephropathy (DN) is a serious kidney disease resulted from diabetes. Dys‐regulated proliferation and extracellular matrix (ECM) accumulation in mesangial cells contribute to DN progression. In this study, we tested expression level of MIAT in DN patients and mesangial cells treated by high glucose (HG). Up‐regulation of MIAT was observed in DN. Then, functional assays displayed that silence of MIAT by siRNA significantly repressed the proliferation and cycle progression in mesangial cells induced by HG. Meanwhile, we found that collagen IV, fibronectin and TGF‐β1 protein expression was obviously triggered by HG, which could be rescued by loss of MIAT. Then, further assessment indicated that MIAT served as sponge harbouring miR‐147a. Moreover, miR‐147a was decreased in DN, which exhibited an antagonistic effect of MIAT on modulating mesangial cell proliferation and fibrosis. Moreover, bioinformatics analysis displayed that E2F transcription factor 3 (E2F3) could act as direct target of miR‐147a. We demonstrated that E2F3 was greatly increased in DN and the direct binding association between miR‐147a and E2F3 was evidenced using luciferase reporter assay. In summary, our data explored the underlying mechanism of DN pathogenesis validated that MIAT induced mesangial cell proliferation and fibrosis via sponging miR‐147a and regulating E2F3.

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Section: Discussionmentioning

confidence: 90%

Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression

et al. 2020

J Cellular Molecular Medi

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“…Previous studies have showed that the ERK1/2 pathway, p38 MAPK pathway and JNK pathway are associated with disc cell apoptosis under stimulation of certain factors [31][32][33][34]. Moreover, these MAPK pathways are also activated under high-glucose conditions in other cells [35,36]. To investigate the signaling pathways behind the effects of high glucose on AF cell apoptosis, we analyzed activity of the JNK pathway and p38 MAPK pathway in AF cells under high-glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.

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“…Emerging evidence has recently suggested that lncR-NAs are essential regulators in the hyperglycemia and pathogenesis of DN, offering a possibility of lncRNAs as potential biomarkers for DN development and progression [22][23][24]. In this study, we were first to uncover that the knockdown of PVT1 ameliorated HG-induced proliferation and fibrosis in human MCs partially through targeting the miR-23b-3p/WT1/NF-κB pathway (Fig.…”

Section: Discussionmentioning

confidence: 91%

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

Zhong

Jiaoe

Xue

et al. 2020

Diabetol Metab Syndr

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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-κB 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-κB pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.

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The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy

Cited by 24 publications

References 48 publications

Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression

Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

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

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