Oncotarget

Research Papers:

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis

Xinguang Yin, Huixing Yi, Linlin Wang, Wanxin Wu, Xiaojun Wu and Linghua Yu _

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Oncotarget. 2016; 7:63767-63778. https://doi.org/10.18632/oncotarget.11654

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Abstract

Xinguang Yin1,2, Huixing Yi3, Linlin Wang4, Wanxin Wu5, Xiaojun Wu2, Linghua Yu2

1Centre for Gastroenterology and Hepatology, The Maternity and Child Health Care Hospital affiliated to Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China

2Centre for Gastroenterology and Hepatology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China

3Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University, Hangzhou, 310009, Zhejiang Province, PR China

4Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China

5Deparment of Pathology, The First Affiliated Hospital of Jiaxing College, Jiaxing, 314001, Zhejiang Province, PR China

Correspondence to:

Linghua Yu, email: [email protected]

Keywords: RSPO, hepatic fibrosis, Wnt pathway, HSC

Received: February 18, 2016     Accepted: August 24, 2016     Published: August 27, 2016

ABSTRACT

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.


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