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TUG1 is involved in liver fibrosis and activation of HSCs by regulating miR-29b

Author:
Han, Xiaohui, Hong, Yuheng, Zhang, Kun
Source:
Biochemical and biophysical research communications 2018 v.503 no.3 pp. 1394-1400
ISSN:
0006-291X
Subject:
gene expression, gene expression regulation, genes, hepatocytes, human diseases, liver, liver cirrhosis, mice, microRNA, microarray technology, patients, proteins, therapeutics, tissues, transcription (genetics)
Abstract:
TUG1 has been shown to be involved in diverse human diseases by regulating gene expression at transcriptional and post-transcriptional levels via interaction with miRNA or proteins. However, the role of TUG1 in liver fibrosis remains unclear. Here, we found that Tug1 is dysregulated in liver fibrosis according to the microarray analysis. Moreover, we investigated the expression files of Tug1 by using CCl4-and BDL-induced liver fibrosis model mice as well as in the primary cells isolated from the mice. We demonstrated that Tug1 is over-expressed in the fibrotic livers and activated HSCs, but not injured hepatocytes. In addition, we assessed the function of Tug1 in HSCs and found that Tug1 promotes the expression of α-SMA, Col1α1, Mmp2/9/10 and Timp1. Mechanically, Tug1 promotes the expression of these pro-fibrogenic genes by down-regulating miR-29b, thus accelerating the progression of liver fibrosis. Further study revealed that TUG1was up-regulated in liver tissues of patients with cirrhosis. All together, our data indicate that TUG1 might be a potential therapy target of liver fibrosis.
Agid:
6093120