GSK3β inhibits epithelial-mesenchymal transition via the Wnt/β-catenin and PI3K/Akt pathways

Zhang, Cheng; Su, Li; Huang, Li

doi:10.18240/ijo.2018.07.08

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…In addition to SMAD-dependent signaling, TGF β induces EMT through SMAD independent signaling pathways including Rho GTPase-dependent pathways ( Lee, Ko & Joo, 2008 ), PI3K/Akt pathway ( Huang et al, 2017 ; Yokoyama et al, 2012 ), mitogen-activated kinase (MAPK) pathways ( Chen et al, 2017 ; Lee et al, 2020 ; Matoba et al, 2017 ; Schiff et al, 2019 ) and Jagged/Notch signaling pathway ( Zhang et al, 2017 ). The MAPK signaling pathways include extracellular signal-regulated kinase(ERK) MAPK pathway, p38 MAPK pathway, and JUN N-terminal kinase (JNK) pathway ( Parrales et al, 2013 ; Schiff et al, 2019 ; Xiao et al, 2014 ; Zhang et al, 2018a ).…”

Section: Survey Methodologymentioning

confidence: 99%

“…The PI3K/Akt pathway mediates a broad range of cellular functions, such as cell transformation, migration, proliferation, apoptosis, and gene expression ( Aguilar-Solis et al, 2017 ; Liu et al, 2019 ). During PVR, binding of TGF-β to its receptor activates PI3K, resulting in the phosphorylation of Akt; activated Akt inhibits glycogen synthase kinase 3β (GSK-3β), promoting EMT in RPE cells ( Shukal et al, 2020 ; Zhang et al, 2018a ). Researchers have found that inhibition or knockdown of GSK-3β promotes cell migration and collagen contraction in ARPE-19 cells, while GSK-3β overexpression and PI3K/Akt inhibitor reverse these cellular responses ( Huang et al, 2017 ).…”

Section: Survey Methodologymentioning

confidence: 99%

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Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Zou

Shan

et al. 2020

PeerJ

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Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

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Section: Survey Methodologymentioning

confidence: 99%

Section: Survey Methodologymentioning

confidence: 99%

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Zou

Shan

et al. 2020

PeerJ

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“…The development of gastric cancer cells was successfully suppressed by pharmacological suppression of Wnt signaling [ 34 ]. Furthermore, cancer cells with an EMT-like phenotype had dysregulated stimulation of the Wnt/catenin pathway, which gave the cancer cells highly metastatic capabilities [ 35 , 36 ]. In Vierge County cells, inhibition of the Wnt pathway by II-spectrin suppressed EMT and invasion.…”

Section: Discussionmentioning

confidence: 99%

Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/β-Catenin Signaling Activation

et al. 2023

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Purpose. Gastric cancer (GC) is one of the most common malignant tumors and also one of the most deadly tumors. In recent years, studies have shown that propofol can inhibit the proliferation and metastasis of many tumor cells. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of GC cells. Methods. Human gastric cancer cell line SGC-7901 and human normal gastric epithelial cell GES-1 were cultured in high-glucose Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% fetal bovine serum at 37°C with 5% CO2. Propofol of different concentrations (0, 2, 5, and 10 μg/mL) was used to treat SGC-7901, and miR-493-3p inhibitor was transfected into SGC-7901. The cell proliferation of SGC-7901 was analyzed by MTT as well as colony formation assay. The qRT-PCR was used to assess the expression of mRNA for key genes. We examined the protein expression of DKK1 and relative markers with western blot. Putative binding places of miR-493-3p on the 3 ′ -untranslated area of DKK1 were predicted using bioinformatics and dual-luciferase method. Results. Propofol prohibited phenotypic features of GC, according to our findings. Furthermore, research into the underlying mechanisms of propofol’s suppressive effects in GC cell proved that propofol therapy improved the degrees of expression of the potential tumor suppressor miR-493-3p. The inhibiting properties of propofol on GC cell development, migration, and invasion were abolished when propofol-induced miR493-3p was silenced with anti-miR-493-3p. We also found that this drug reversed epithelial-mesenchymal transformation in SGC-7901 cells via inducing miR-493-3p. Propofol-induced miR-493-3p decreases GC cell development via targeting DKK1 and hence inhibits Wnt/β-catenin signaling, according to these findings. Conclusion. Propofol-induced miR-493-3p decreased GC cell development via targeting DKK1 and hence inhibited Wnt/β-catenin signaling, according to these findings.

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“…Additionally, FN1 was found to be one of the most abundant transcripts in an analysis of human PVR epiretinal membranes [ 45 ]. Vimentin and Col1A1 transcripts were upregulated in human PVR membranes [ 45 ], and Vimentin levels were also found to be increased in a rabbit model of PVR [ 46 ]. Glial fibrillary acidic protein (GFAP) has also been detected in epiretinal membranes removed from PVR patients [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model

et al. 2020

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Proliferative vitreoretinopathy (PVR) is a progressive disease that develops in a subset of patients who undergo surgery for retinal detachment repair, and results in significant vision loss. PVR is characterized by the migration of retinal pigment epithelial (RPE) cells into the vitreous cavity, where they undergo epithelial-to-mesenchymal transition and form contractile membranes within the vitreous and along the retina, resulting in recurrent retinal detachments. Currently, surgical intervention is the only treatment for PVR and there are no pharmacological agents that effectively inhibit or prevent PVR formation. Here, we show that a single intravitreal injection of the polyether ionophore salinomycin (SNC) effectively inhibits the formation of PVR in a mouse model with no evidence of retinal toxicity. After 4 weeks, fundus photography and optical coherence tomography (OCT) demonstrated development of mean PVR grade of 3.5 (SD: 1.3) in mouse eyes injected with RPE cells/DMSO (vehicle), compared to mean PVR grade of 1.6 (SD: 1.3) in eyes injected with RPE cells/SNC (p = 0.001). Additionally, immunohistochemistry analysis showed RPE cells/SNC treatment reduced both fibrotic (αSMA, FN1, Vim) and inflammatory (GFAP, CD3, CD20) markers compared to control RPE cells/DMSO treatment. Finally, qPCR analysis confirmed that Tgfβ, Tnfα, Mcp1 (inflammatory/cytokine markers), and Fn1, Col1a1 and Acta2 (fibrotic markers) were significantly attenuated in the RPE cells/SNC group compared to RPE/DMSO control. These results suggest that SNC is a potential pharmacologic agent for the prevention of PVR in humans and warrants further investigation.

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GSK3β inhibits epithelial-mesenchymal transition via the Wnt/β-catenin and PI3K/Akt pathways

Abstract: GSK3β effectively inhibits EMT the Wnt/β-catenin and PI3K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.

Cited by 14 publications

References 25 publications

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/β-Catenin Signaling Activation

Salinomycin inhibits proliferative vitreoretinopathy formation in a mouse model

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