MiR-9a-5p regulates proliferation and migration of hepatic stellate cells under pressure through inhibition of Sirt1.
World J Gastroenterol
; 21(34): 9900-15, 2015 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-26379395
AIM: To reveal the functions of microRNAs (miRNAs) with respect to hepatic stellate cells (HSCs) in response to portal hypertension. METHODS: Primary rat HSCs were exposed to static water pressure (10 mmHg, 1 h) and the pressure-induced miRNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of miRNAs. A potential target of MiR-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure. RESULTS: According to the profile, the expression of miR-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs (3.70 ± 0.61 vs 0.97 ± 0.15, P = 0.0226), which resulted in the proliferation, migration and activation of HSCs. In vivo, the up-regulation of miR-9a-5p (2.09 ± 0.91 vs 4.27 ± 1.74, P = 0.0025) and the down-regulation of Sirt1 (2.41 ± 0.51 vs 1.13 ± 0.11, P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of miR-9a-5p. Through restoring the expression of Sirt1 in miR-9a-5p transfected HSCs on pressure overload, we found that overexpression of Sirt1 could partially abrogate the miR-9a-5p mediated suppression of the proliferation, migration and activation of HSCs. CONCLUSION: Our results suggest that during liver fibrosis, portal hypertension may induce the proliferation, migration and activation of HSCs through the up-regulation of miR-9a-5p, which targets Sirt1.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Pressão na Veia Porta
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MicroRNAs
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Mecanotransdução Celular
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Proliferação de Células
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Células Estreladas do Fígado
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Sirtuína 1
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Hipertensão Portal
Limite:
Animals
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China