Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells.
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.
Molecular and Cellular Glycobiology Unit, Department of Biological Science, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
Seok-Jo
SJ
Kim
Tae-Wook
TW
Chung
Hee-Jung
HJ
Choi
Choong-Hwan
CH
Kwak
Kwon-Ho
KH
Song
Seok-Jong
SJ
Suh
Kyung-Min
KM
Kwon
Young-Chae
YC
Chang
Young-Guk
YG
Park
Hyeun Wook
HW
Chang
Kyoung-Sook
KS
Kim
Cheorl-Ho
CH
Kim
Young-Choon
YC
Lee
D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D012799:Sialyltransferases / Q000737:chemistry* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000502:physiology*
D053773:Transforming Growth Factor beta1; D012799:Sialyltransferases; C021343:haematoside synthetase