Cryptolepine derivative-6h inhibits liver fibrosis in TGF-ß1-induced HSC-T6 cells by targeting the Shh pathway.
Can J Physiol Pharmacol
; 94(9): 987-95, 2016 Sep.
Article
en En
| MEDLINE
| ID: mdl-27295431
ABSTRACT
Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-ß1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-ß1-induced HSC-T6 cells.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Factor de Crecimiento Transformador beta1
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Proteínas Hedgehog
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Células Estrelladas Hepáticas
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Cirrosis Hepática
Límite:
Animals
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Humans
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2016
Tipo del documento:
Article
País de afiliación:
China