Statins reduce TGF-beta2-modulation of the extracellular matrix in cultured astrocytes of the human optic nerve head.
Exp Eye Res
; 164: 55-63, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-28789942
ABSTRACT
Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-ß2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-ß2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1. Suppression of ECM related proteins is due to inhibition of Smad2/3 activation as statins inhibit TGF-ß2-induced Smad2 phosphorylation and Smad2/3 nuclear accumulation. In ONH astrocytes, TGF-ß2 does not induce MAPK activation. In this study we found an anti-fibrotic effect of statins in human astrocytes of the ONH and identified TGF-ß2 as a mediator of statin action, which may support a beneficial role for statins in blocking glaucomatous axonal damage induced by ECM remodeling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Disco Óptico
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Astrócitos
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Matriz Extracelular
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Fator de Crescimento Transformador beta2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Eye Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Coréia do Sul