Loading…

PAX6 contributes to the activation and proliferation of hepatic stellate cells via activating Hedgehog/GLI1 pathway

Aberrant activation of Hedgehog signaling is considered as the key player in hepatic stellate cell (HSC) activation involved in liver fibrosis (LF). The glioma-associated protein gene (GLI) has a predicted paired box 6 (PAX6)-binding site within its transcribed region. Therefore, this study aimed to...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-05, Vol.526 (2), p.314-320
Main Authors: Li, Can, Tan, Yue Hao, Sun, Jing, Deng, Feng Mei, Liu, Yi Lun
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aberrant activation of Hedgehog signaling is considered as the key player in hepatic stellate cell (HSC) activation involved in liver fibrosis (LF). The glioma-associated protein gene (GLI) has a predicted paired box 6 (PAX6)-binding site within its transcribed region. Therefore, this study aimed to investigate the relationship between PAX6 and GLI and their contribution to HSC activation and proliferation. PAX6 expression was upregulated in platelet-derived growth factor-BB (PDGF-BB)-induced LX-2 cells. The activation and proliferation of HSC were inhibited by interference of PAX6 with short hairpin RNA (shPAX6) via curbing Hedgehog signaling. Notably, PAX6 directly bound to the promoter sequence of GLI1 independent of the PTCH/SMO axis. Therefore, we propose that PAX6 upregulation induces HSC activation and proliferation through crosstalk with GLI1 signaling. Thus, these novel mechanistic insights involving the PAX6-mediated regulation of the activation and proliferation of HSC may provide a new therapeutic target for LF. Diagram representing the potential mechanism by which PAX6 regulates Hedgehog signalling activation in HSCs. Based on our findings, PAX6 expression is upregulated in PDGF-BB-induced LX-2 cells, and PAX6 promotes the activation and proliferation of HSCs. Moreover, PAX6 directly binds to the proximal promoter region of GLI1. Thereafter, the Hedgehog signalling pathway is activated, which promotes HSCs activation and proliferation. [Display omitted] •PAX6 is up-regulated in activated hepatic stellate cells (HSCs).•Silencing PAX6 can inhibit HSC activation and proliferation.•PAX6 directly binds to GLI1 promoter sequence independent of PTCH/SMO axis.•PAX6 promotes HSC activation and proliferation by inducing Hedgehog/GLI1 signaling.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.03.086