Crosstalk between TGFß and Wnt signaling pathways in the human trabecular meshwork.
Exp Eye Res
; 148: 97-102, 2016 07.
Article
en En
| MEDLINE
| ID: mdl-27091054
ABSTRACT
Primary Open Angle Glaucoma (POAG) is an irreversible, vision-threatening disease that affects millions worldwide. The principal risk factor of POAG is increased intraocular pressure (IOP) due to pathological changes in the trabecular meshwork (TM). The TGFß signaling pathway activator TGFß2 and the Wnt signaling pathway inhibitor secreted frizzled-related protein 1 (sFRP1) are elevated in the POAG TM. In this study, we determined whether there is a crosstalk between the TGFß/Smad pathway and the canonical Wnt pathway using luciferase reporter assays. Lentiviral luciferase reporter vectors for studying the TGFß/Smad pathway or the canonical Wnt pathway were transduced into primary human non-glaucomatous TM (NTM) cells. Cells were treated with or without a combination of 5 µg/ml TGFß2 and/or 100 ng/ml Wnt3a recombinant proteins, and luciferase levels were measured using a plate reader. We found that TGFß2 inhibited Wnt3a-induced canonical Wnt pathway activation, while Wnt3a inhibited TGFß2-induced TGFß/Smad pathway activation (n = 6, p < 0.05) in 3 NTM cell strains. We also found that knocking down of Smad4 or ß-catenin using siRNA in HTM5 cells transfected with similar luciferase reporter plasmids abolished the inhibitory effect of TGFß2 and/or Wnt3a on the other pathway (n = 6). Our results suggest the existence of a cross-inhibition between the TGFß/Smad and canonical Wnt pathways in the TM, and this cross-inhibition may be mediated by Smad4 and ß-catenin.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Malla Trabecular
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Glaucoma de Ángulo Abierto
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Factor de Crecimiento Transformador beta2
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Proteína Wnt3A
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Vía de Señalización Wnt
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Exp Eye Res
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos