Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells

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

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalBiochemical Journal
Volume449
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

G(M3) Ganglioside
Epithelial-Mesenchymal Transition
Transforming Growth Factors
Lenses
Epithelial Cells
Cell Movement
Genes
Glycosphingolipids
Growth Factor Receptors
N-Acetylneuraminic Acid
Cell membranes
Reporter Genes
Small Interfering RNA
Transcriptional Activation
Insulin Resistance
Tumors
Chemical activation

Keywords

  • Ganglioside GM3
  • Lens epithelial cell
  • Transcriptional regulation
  • Transforming growth factor β1 receptor (TGFβR)
  • Transforming growth factor-β1-induced epithelial-mesenchymal transition (TGF-β1-induced EMT)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, Seok Jo ; Chung, Tae Wook ; Choi, Hee Jung ; Kwak, Choong Hwan ; Song, Kwon Ho ; Suh, Seok Jong ; Kwon, Kyung Min ; Chang, Young Chae ; Park, Young Guk ; Chang, Hyeun Wook ; Kim, Kyoung Sook ; Kim, Cheorl Ho ; Lee, Young Choon. / Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells. In: Biochemical Journal. 2013 ; Vol. 449, No. 1. pp. 241-251.
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abstract = "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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author = "Kim, {Seok Jo} and Chung, {Tae Wook} and Choi, {Hee Jung} and Kwak, {Choong Hwan} and Song, {Kwon Ho} and Suh, {Seok Jong} and Kwon, {Kyung Min} and Chang, {Young Chae} and Park, {Young Guk} and Chang, {Hyeun Wook} and Kim, {Kyoung Sook} and Kim, {Cheorl Ho} and Lee, {Young Choon}",
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Kim, SJ, Chung, TW, Choi, HJ, Kwak, CH, Song, KH, Suh, SJ, Kwon, KM, Chang, YC, Park, YG, Chang, HW, Kim, KS, Kim, CH & Lee, YC 2013, 'Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells', Biochemical Journal, vol. 449, no. 1, pp. 241-251. https://doi.org/10.1042/BJ20120189

Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells. / Kim, Seok Jo; Chung, Tae Wook; Choi, Hee Jung; Kwak, Choong Hwan; Song, Kwon Ho; Suh, Seok Jong; Kwon, Kyung Min; Chang, Young Chae; Park, Young Guk; Chang, Hyeun Wook; Kim, Kyoung Sook; Kim, Cheorl Ho; Lee, Young Choon.

In: Biochemical Journal, Vol. 449, No. 1, 01.01.2013, p. 241-251.

Research output: Contribution to journalArticle

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T1 - Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells

AU - Kim, Seok Jo

AU - Chung, Tae Wook

AU - Choi, Hee Jung

AU - Kwak, Choong Hwan

AU - Song, Kwon Ho

AU - Suh, Seok Jong

AU - Kwon, Kyung Min

AU - Chang, Young Chae

AU - Park, Young Guk

AU - Chang, Hyeun Wook

AU - Kim, Kyoung Sook

AU - Kim, Cheorl Ho

AU - Lee, Young Choon

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N2 - 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.

AB - 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.

KW - Ganglioside GM3

KW - Lens epithelial cell

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KW - Transforming growth factor β1 receptor (TGFβR)

KW - Transforming growth factor-β1-induced epithelial-mesenchymal transition (TGF-β1-induced EMT)

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