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
in En
| MEDLINE
| ID: mdl-26379395
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Movement
/
Portal Pressure
/
MicroRNAs
/
Mechanotransduction, Cellular
/
Cell Proliferation
/
Hepatic Stellate Cells
/
Sirtuin 1
/
Hypertension, Portal
Limits:
Animals
Language:
En
Journal:
World J Gastroenterol
Journal subject:
GASTROENTEROLOGIA
Year:
2015
Document type:
Article
Affiliation country:
China