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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2015 ; 5
(ä): 16163
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MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in
nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a
#MMPMID26537990
Du J
; Niu X
; Wang Y
; Kong L
; Wang R
; Zhang Y
; Zhao S
; Nan Y
Sci Rep
2015[Nov]; 5
(ä): 16163
PMID26537990
show ga
Nonalcoholic fibrosing steatohepatitis is a uniform process throughout
nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested
to modulate cellular processes in liver diseases. However, the functional role of
miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this
study, we systematically analyzed the hepatic miRNAs by microarray analysis in
nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by
methionine-choline deficient (MCD) diet. We identified 19 up-regulated and 18
down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs,
miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity
assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p.
Hepatic miR-146a-5p was down-regulated in fibrosing steatohepatitis, but its
target genes Wnt1 and Wnt5a and their consequent effectors ?-SMA and Col-1 were
significantly up-regulated. In addition, miR-146a-5p was downregulated, whilst
Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells
(HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in
HSCs inhibited HSC activation and proliferation, which concomitant with the
decreased expressions of Wnt1, Wnt5a, ?-SMA and Col-1. In conclusion, miR-146a-5p
suppresses activation and proliferation of HSCs in the progress of nonalcoholic
fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent
effectors ?-SMA and Col-1.