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.
Ganglioside GM3 participates in the TGF-β1-induced epithelial–mesenchymal transition of human lens epithelial cells
- Views Icon Views
- Share Icon Share
Seok-Jo Kim, Tae-Wook Chung, Hee-Jung Choi, Choong-Hwan Kwak, Kwon-Ho Song, Seok-Jong Suh, Kyung-Min Kwon, Young-Chae Chang, Young-Guk Park, Hyeun Wook Chang, Kyoung-Sook Kim, Cheorl-Ho Kim, Young-Choon Lee; Ganglioside GM3 participates in the TGF-β1-induced epithelial–mesenchymal transition of human lens epithelial cells. Biochem J 1 January 2013; 449 (1): 241–251. doi: https://doi.org/10.1042/BJ20120189
Download citation file: