Lutein targeting orbital fibroblasts attenuates fibrotic and inflammatory effects in thyroid-associated ophthalmopathy.
Exp Eye Res
; 232: 109515, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-37207866
ABSTRACT
Lutein (LU) is a carotenoid that has recently been implicated in multiple roles in fibrosis, inflammation, and oxidative stress. Thyroid-associated ophthalmopathy (TAO) is particularly relevant to these pathological changes. We thus aim to probe the potential therapeutic effects of TAO in an in vitro model. We used LU pre-treating OFs derived from patients with TAO or not, then treated with TGF-ß1(or IL-1ß)to induce fibrosis (or inflammation). We analyzed the different expressions of related genes and proteins, and the molecular mechanism pathway on TAO OFs was screened by RNA sequencing, which is identified in vitro. We found that LU attenuates fibrotic and inflammatory effects in TAO. LU inhibited ACTA2, COL1A1, FN1, and CTGF mRNA expression and suppressed α-SMA, and FN1 protein expression induced by TGF-ß1. Besides, LU suppressed OFs migration. Besides, it is shown that LU suppressed inflammation-related genes, such as IL-6, IL-8, CXCL1, and MCP-1. Moreover, LU inhibited oxidative stress induced by IL-1ß, which is analyzed by DHE fluorescent probe staining. RNA sequencing suggested ERK/AP-1 pathway may be the molecular mechanism of LU protective effect on TAO, which is identified by RT-qPCR and western-blot. In summary, this study provides the first evidence that LU significantly attenuates the pathogenic manifestations of TAO by inhibiting the expression of fibrotic and inflammation-related genes and ROS produced by OFs. These data suggested that LU may be a potential medicine for TAO.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oftalmopatia de Graves
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Eye Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China