PAX6 contributes to the activation and proliferation of hepatic stellate cells via activating Hedgehog/GLI1 pathway
| Autor: | Can Li, Feng Mei Deng, Jing Sun, Yue Hao Tan, Yi-Lun Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Liver Cirrhosis
0301 basic medicine PAX6 Transcription Factor Biophysics Zinc Finger Protein GLI1 Biochemistry Cell Line Small hairpin RNA 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation GLI1 Hepatic Stellate Cells Humans Hedgehog Proteins Molecular Biology Hedgehog Cell Proliferation biology Chemistry Cell Biology Hedgehog signaling pathway Cell biology Crosstalk (biology) 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Hepatic stellate cell sense organs PAX6 Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 526:314-320 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.03.086 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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