● AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. ● METHODS: Experimental P...● AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. ● METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium(RPE) cells in the eyes of rabbits. A PI3 K/Akt inhibitor(wortmannin) and a GSK3β inhibitor(Li Cl) were also injected at different time during PVR progress. Electroretinogram(ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling(TUNEL) assay. The vitreous was also collected for metabolomic analysis.● RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. ● CONCLUSION: GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.展开更多
基金Supported by the National Natural Science Foundation of China(No.81371039)Shanghai Natural Science Foundation(No.18ZR1440200)
文摘● AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. ● METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium(RPE) cells in the eyes of rabbits. A PI3 K/Akt inhibitor(wortmannin) and a GSK3β inhibitor(Li Cl) were also injected at different time during PVR progress. Electroretinogram(ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling(TUNEL) assay. The vitreous was also collected for metabolomic analysis.● RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. ● CONCLUSION: GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.
