Morin attenuates diethylnitrosamine-induced rat liver fibrosis and hepatic stellate cell activation by co-ordinated regulation of Hippo/Yap and TGF-ß1/Smad signaling.
Biochimie
; 140: 10-19, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28552397
ABSTRACT
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-ß1 (TGF-ß1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-ß1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/ß-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-ß1/Smad pathways was not determined. To address this concern, this study was carried out in cultured LX-2 cells and diethylnitrosamine-induced fibrotic rats. Morin activated hippo signaling through significantly increased expression of Mst1 and Lats1 with decreased expression of transcriptional effectors Yap/TAZ, thereby prevented HSC activation and also suppressed the expression of exacerbated TGF-ß/Smad signaling molecules such as TGF-ß1, p-Smad2/3, collagen-I, MMP-2, MMP-9 and TIMP-1 in cultured LX-2 and DEN induced fibrotic rats. Both the in vitro and in vivo results clearly showed that, morin by acting on Hippo/Yap and TGF-ß1/Smad pathways, ameliorated experimental liver fibrosis, indicating that morin has potential for effective treatment of liver fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Transdução de Sinais
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Proteínas Serina-Treonina Quinases
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Dietilnitrosamina
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Proteína Smad2
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Proteína Smad3
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Proteínas Reguladoras de Apoptose
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Fator de Crescimento Transformador beta1
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Células Estreladas do Fígado
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Cirrose Hepática
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochimie
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia