Silencing CCNG1 protects MPC-5 cells from high glucose-induced proliferation-inhibition and apoptosis-promotion via MDM2/p53 signaling pathway

Chen, Ye; Yan, Rui; Li, Bo; Li, Jun; Liu, Xiaoxia; Song, Wenyu; Zhu, Chunling

doi:10.1007/s11255-020-02383-4

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…Functionally, CCNG1 overexpression restored lncRNA MSC-AS1 knockdown-inhibited HRMC cell proliferation, fibrosis, and inflammation. Consistent with our results, Chen et al reported that downregulation of CCNG1 had a protective effect on DN, and its mechanism was related to the MDM2-p53 pathway [13]. All these findings emphasize that CCNG1 is the pathogenic factor of DN.…”

Section: Discussionsupporting

confidence: 93%

“…MiR-122-5p inhibited cell proliferation, migration, and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma [ 12 ]. Moreover, silencing CCNG1 has been found to protect MPC-5 cells from HG-induced proliferation inhibition and apoptosis promotion through the MDM2/ p 53 signaling pathway [ 13 ]. However, the regulatory mechanism of lncRNA MSC-AS1/miR-325/CCNG1 in DN is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

Zhao

Cui

Dong³

et al. 2022

Journal of Healthcare Engineering

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Background. Diabetic nephropathy (DN) is the most common microvascular complication of diabetes and has become the second leading cause of end-stage renal disease in the world. This study aims to clarify the regulatory mechanism of the lncRNA MSC-AS1/miR-325/cyclin G1 (CCNG1) axis in DN. Methods. The regulatory mechanism of lncRNA MSC-AS1/miR-325/CCNG1 was evaluated by RT-qPCR, CCK-8 assay, flow cytometry assay, RNA pull-down assay, ELISA, and western blot assay. Results. Upregulation of lncRNA MSC-AS1 was detected in DN patients and HRMC cells treated with high glucose (HG). Knockdown of lncRNA MSC-AS1 reduced the proliferation, fibrosis, and inflammation of HRMC cells induced by HG. In addition, lncRNA MSC-AS1 acts as a miR-325 sponge in the DN. CCNG1 is the direct target of miR-325, which can be positively regulated by lncRNA MSC-AS1 in DN. More importantly, downregulation of miR-325 and upregulation of CCNG1 can attenuate the protective effect of lncRNA MSC-AS1 knockdown on DN. Conclusion. lncRNA MSC-AS1 aggravates DN by downregulating miR-325 and upregulating CCNG1.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

Zhao

Cui

Dong³

et al. 2022

Journal of Healthcare Engineering

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“…30 In the current study, HG exposure markedly interfered with MPC-5 cell viability and intensified the percentage of apoptotic cells, which is consistent with the results of previous studies. 31,32 Importantly, FA treatment dose-dependently improved the impact of HG induction on MPC-5 cells, suggesting the protective effect of FA on podocytes under HG condition.…”

Section: Discussionmentioning

confidence: 90%

Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition

Quan¹,

Liu²,

Ye³

et al. 2021

DMSO

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Background Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms. Methods MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling. Results Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression. Conclusion These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.

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“…Huang et al reported that notoginsenoside R1 could activate the PI3K-Akt signalling pathway to exert anti-apoptotic and renalprotective effects in DN mice [83]. p53 is a transcription factor, and the main outcomes of its activation are cell cycle arrest and apoptosis [84]. Evidence suggests that p53 overexpression is associated with the progression of DN, as p53 mediates podocyte apoptosis related to DN and promotes the expression of pro-fibrotic genes such as plasminogen activator inhibitor-1 [85][86][87].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking technology-based predictive study of the active ingredients and potential targets of rhubarb for the treatment of diabetic nephropathy

Zhou

et al. 2022

BMC Complement Med Ther

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Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the main cause of end-stage renal failure. Rhubarb is a widely used traditional Chinese herb, and it has exhibited efficacy in reducing proteinuria, lowering blood sugar levels and improving kidney function in patients with DN. However, the exact pharmacological mechanism by rhubarb improves DN remain unclear due to the complexity of its ingredients. Hence, we systematically explored the underlying mechanisms of rhubarb in the treatment of DN. We adopted a network pharmacology approach, focusing on the identification of active ingredients, drug target prediction, gene collection, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking technology was used to verify the binding ability between the main active compounds and central therapeutic targets, and screen out the core active ingredients in rhubarb for the treatment of DN. Finally, molecular dynamics simulation was performed for the optimal core protein-ligand obtained by molecular docking using GROMACS software. The network analysis identified 16 active compounds in rhubarb that were linked to 37 possible therapeutic targets related to DN. Through protein–protein interaction analysis, TP53, CASP8, CASP3, MYC, JUN and PTGS2 were identified as the key therapeutic targets. By validation of molecular docking, finding that the central therapeutic targets have good affinities with the main active compounds of rhubarb, and rhein, beta-sitosterol and aloe-emodin were identified as the core active ingredients in rhubarb for the treatment of DN. Results from molecular dynamics simulations showed that TP53 and aloe-emodin bound very stably with a binding free energy of − 26.98 kcal/mol between the two. The results of the gene enrichment analysis revealed that the PI3K-Akt signalling pathway, p53 signalling pathway, AGE-RAGE signalling pathway and MAPK signalling pathway might be the key pathways for the treatment of DN, and these pathways were involved in podocyte apoptosis, glomerular mesangial cell proliferation, inflammation and renal fibrosis. Based on the network pharmacology approach and molecular docking technology, we successfully predicted the active compounds and their respective targets. In addition, we illustrated the molecular mechanisms that mediate the therapeutic effects of rhubarb against DN. These findings provided an important scientific basis for further research of the mechanism of rhubarb in the treatment of DN.

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Silencing CCNG1 protects MPC-5 cells from high glucose-induced proliferation-inhibition and apoptosis-promotion via MDM2/p53 signaling pathway

Cited by 11 publications

References 30 publications

lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition

Network pharmacology and molecular docking technology-based predictive study of the active ingredients and potential targets of rhubarb for the treatment of diabetic nephropathy

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