Activation of autophagy inhibits epithelial to mesenchymal transition process of human lens epithelial cells induced by high glucose conditions

2020 ◽  
Vol 75 ◽  
pp. 109768 ◽  
Author(s):  
Ji Li ◽  
Wei Ye ◽  
Wenqin Xu ◽  
Tianfang Chang ◽  
Luning Zhang ◽  
...  
2021 ◽  
Vol 14 (7) ◽  
pp. 965-972
Author(s):  
Qing Liu ◽  
◽  
Hong Yan ◽  

AIM: To study the effect of thioltransferase (TTase) on oxidative stress in human lens epithelial cells (HLECs) induced by high glucose and advanced glycation end products (AGEs). METHODS: HLECs were treated with 35.5 mmol/L glucose or 1.5 mg/mL AGEs modified bovine serum albumin (AGEs-BSA) as the experimental groups, respectively. Cells were collected at the time point of 1, 2, 3, and 4d. The TTase activity were measured accordingly. TTase mRNA levels were detected by quantitative reverse transcription polymerase chain response (qRT-RCR) and its protein level was detected by Western blot. The siRNA was used to knock down the expression of TTase. The activity of catalase (CAT) and superoxide dismutase (SOD), the content of reactive oxygen species (ROS) and the ratio of oxidized glutathione/total glutathione (GSSG/T-GSH) were assessed in different groups, respectively. RESULTS: The level of TTase mRNA gradually increased and reached the top at 2d, then it decreased to the normal level at 4d, and the TTase activity increased from 2 to 3d in both high glucose and AGEs-BSA groups. The TTase expression elevated from 2d in high glucose group, and it began to rise from 3d in AGEs-BSA group. The activity of CAT and SOD showed a decrease and the content of ROS and the ratio of GSSG/T-GSH showed an increase in high glucose and AGEs-BSA group. These biochemical alterations were more prominent in the groups with TTase siRNA. CONCLUSION: High glucose and AGEs can increase ROS content in HLECs; therefore, it induces oxidative stress. This may result in the decreased GSH and increased GSSG content, impaired activity of SOD and CAT. The up-regulated TTase likely provides oxidation damage repair induced by high glucose and AGEs in the early stage.


2012 ◽  
Vol 449 (1) ◽  
pp. 241-251 ◽  
Author(s):  
Seok-Jo Kim ◽  
Tae-Wook Chung ◽  
Hee-Jung Choi ◽  
Choong-Hwan Kwak ◽  
Kwon-Ho Song ◽  
...  

TGF-β (transforming growth factor-β)-induced EMT (epithelial–mesenchymal transition) induces the proliferation and migration of the HLE (human lens epithelial) cells. Ganglioside GM3, simple sialic-acid-containing glycosphingolipids on mammalian cell membranes, regulates various pathological phenomena such as insulin resistance and tumour progression. However, the relationship between ganglioside GM3 and TGF-β-induced EMT in the HLE B-3 cells is poorly understood. In the present study we demonstrated that ganglioside GM3 was involved in TGF-β1-induced EMT in HLE B-3 cells. Our results indicated that the expression of ganglioside GM3 and GM3 synthase mRNA were significantly increased in TGF-β1-induced HLE B-3 cells. Reporter gene analysis also demonstrated that transcriptional activation of the GM3 synthase gene was regulated by Sp1 (specificity protein 1) in HLE B-3 cells upon TGF-β1 stimulation. Interestingly, the inhibition of ganglioside GM3 expression by d-PDMP [d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol] and GM3 synthase shRNA (short hairpin RNA) resulted significantly in the suppression of cell migration and EMT-related signalling in HLE B-3 cells stimulated by TGF-β. Furthermore, exogenous treatment of ganglioside GM3 rescued the expression of EMT molecules and cell migration suppressed by the depletion of ganglioside GM3 in TGF-β1-induced HLE B-3 cells. We also found that ganglioside GM3 interacted with TGFβRs (TGF-β receptors) in TGF-β1-induced HLE B-3 cells. Taken together, these results suggest that ganglioside GM3 induced by TGF-β1 regulates EMT by potential interaction with TGFβRs.


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