The role of HIF-1α in the TGF-ß2-mediated epithelial-to-mesenchymal transition of human lens epithelial cells.
J Cell Biochem
; 119(8): 6814-6827, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29693273
ABSTRACT
Human lens epithelial cells (HLE) undergo mesenchymal transition and become fibrotic during posterior capsule opacification (PCO), which is a frequent complication after cataract surgery. TGF-ß2 has been implicated in this fibrosis. Previous studies have focused on the role of hypoxia-inducible factor-1α (HIF-1α) in fibrotic diseases, but the role of HIF-1α in the TGF-ß2-mediated fibrosis in HLE is not known. TGF-ß2 treatment (10 ng/mL, 48 h) increased the HIF-1α levels along with the EMT markers in cultured human lens epithelial cells (FHL124 cells). The increase in HIF-1α corresponded to an increase in VEGF-A in the culture medium. However, exogenous addition of VEGF-A (up to 10 ng/mL) did not alter the EMT marker levels in HLE. Addition of a prolyl hydroxylase inhibitor, dimethyloxalylglycine (DMOG, up to 10 µM), enhanced the levels of HIF-1α, and secreted VEGF-A but did not alter the EMT marker levels. However, treatment of cells with a HIF-1α translational inhibitor, KC7F2, significantly reduced the TGF-ß2-mediated EMT response. This was accompanied by a reduction in the ERK phosphorylation and nuclear translocation of Snail and Slug. Together, these data suggest that HIF-1α is important for the TGF-ß2-mediated EMT of human lens epithelial cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MAP Kinase Signaling System
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Epithelial Cells
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Hypoxia-Inducible Factor 1, alpha Subunit
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Transforming Growth Factor beta2
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Eye Proteins
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Capsule Opacification
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Epithelial-Mesenchymal Transition
Limits:
Humans
Language:
En
Journal:
J Cell Biochem
Year:
2018
Type:
Article