Y-box Protein-1 Regulates the Expression of Collagen I in Hepatic Progenitor Cells via PDGFR-β/ERK/p90RSK Signalling.

Fei Li,Xiaobo Cai,Ying Qu,Zhenzeng Ma,Lungen Lu,Heng Liu,Qidi Zhang,Mingyi Xu

doi:10.1155/2017/6193106

Abstract

Y-box protein-1 (YB-1) is a highly conserved transcription factor that is involved in multiple biological processes via transcriptional regulation of several genes, including p53, cyclin D1, and EGFR. YB-1 has been reported to be overexpressed in injured livers. This study aims to explore the functions of YB-1 in hepatic progenitor cells (HPCs). Herein, chromatin immunoprecipitation sequencing (ChIP-sequencing) and RNA-sequencing assays identified that YB-1 participated in the biological adhesion process and ECM-receptor interactions in HPCs. Further study demonstrated that YB-1 modulated the expression of extracellular matrix components in HPCs. ChIP-sequencing assays established that PDGFR-β was a target gene of YB-1, and luciferase reporter assays confirmed that YB-1 negatively regulated PDGFR-β promoter activity in HPCs. In addition, PDGFR-β can regulate the expression of collagen I through ERK/p90RSK signalling, and disruption of the signalling pathway with a PDGFR-β inhibitor or ERK1/2 inhibitor abolished the regulatory effect of PDGFR-β on collagen I expression in HPCs. Conclusively, YB-1 can modulate the expression of collagen I in HPCs via direct binding to the PDGFR-β promoter, negatively regulating its expression. In addition, the ERK/p90RSK axis serves as the downstream signalling pathway of PDGFR-β.

Highlights

Y-box protein-1 (YB-1) belongs to a family of DNA- and RNA-binding factors, named cold shock proteins, which are highly conserved during evolution and have been shown to function as regulators of gene transcription and translation
YB-1 has been found to bind to a number of genes, including cyclin D1, epithermal growth factor receptor (EGFR), and mitogen-activated protein kinase-interacting kinase 1 (MNK1), and modulate the transcription of these genes and the proliferation rate of related tumour cells [4,5,6]
To clarify the biological functions of YB-1, we analysed the genome-wide binding sites of YB-1 in hepatic progenitor cells (HPCs) using chromatin immunoprecipitation coupled with high-throughput deep sequencing (ChIP sequencing)

Summary

Introduction

YB-1 belongs to a family of DNA- and RNA-binding factors, named cold shock proteins, which are highly conserved during evolution and have been shown to function as regulators of gene transcription and translation. A large number of studies regarding the functions of YB-1 were conducted, and they demonstrated multiple effects of YB-1 on cell proliferation, migration, and transformation. YB-1 has been found to bind to a number of genes, including cyclin D1, epithermal growth factor receptor (EGFR), and mitogen-activated protein kinase-interacting kinase 1 (MNK1), and modulate the transcription of these genes and the proliferation rate of related tumour cells [4,5,6]. In human embryonic kidney cells and dermal fibroblasts, YB-1 exerted a repressive effect on the collagen α1 (I) (COL1A1) and matrix metalloproteinase-2 (MMP-2) gene promoters [7, 8]

Objectives

Methods

Results

Conclusion