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学科主题: 临床医学
题名:
In vitro interactions between rat bone marrow-derived endothelial progenitor cells and hepatic stellate cells
作者: Liu, Feng; Liu, Zhi-da; Wu, Nan; Wang, Jiang-Hua; Zhang, Heng-Hui; Fei, Ran; Cong, Xu; Chen, Hong-song; Wei, Lai
关键词: Endothelial progenitor cell ; Hepatic stellate cells ; Coculture ; Apoptosis ; Proliferation ; Differentiation
刊名: IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
发表日期: 2013-08-01
DOI: 10.1007/s11626-013-9637-x
卷: 49, 期:7, 页:537-547
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Developmental Biology
研究领域[WOS]: Cell Biology ; Developmental Biology
关键词[WOS]: LIVER-CIRRHOSIS ; GROWTH-FACTOR ; STEM-CELLS ; REGENERATION ; ACTIVATION ; FIBROGENESIS ; FIBROSIS ; THERAPY
英文摘要:

Transplantation of bone marrow (BM)-derived endothelial progenitor cells (EPCs) has been reported to improve liver fibrosis, but there is no direct evidence for the mechanism of improvement. We investigated the mechanism in vitro by coculturing BM-derived EPCs with activated hepatic stellate cells (HSCs) to mimic the hepatic environment. EPCs and HSCs were cultured alone and indirectly cocultured at a 1:1 ratio in a Transwell system. The characteristics of HSCs and EPCs were examined at different time points. An invasion assay showed the time-dependent effect on degradation of the extracellular matrix (ECM) layer in EPCs cultured alone. Real-time PCR and enzyme-linked immunosorbent assay analysis revealed that EPCs served as a source of matrix metalloproteinase-9 (MMP-9), and MMP-9 expression levels significantly increased during the 2 d of coculture. CFSE labeling showed that EPCs inhibited proliferation of HSCs. Annexin-V/PI staining, erminal deoxynucleotidyl transferase X-dUTP nick end labeling analysis, and (cleaved) caspase-3 activity revealed that EPCs promoted HSC apoptosis. However, the proliferation and apoptosis of EPCs were unaffected by cocultured HSCs. Coculturing increased the expression of inducible nitric oxide synthase, vascular endothelial growth factor, and hepatocyte growth factor (HGF) in EPCs, promoted differentiation of EPCs, and reduced the expression of types I and III collagens and transforming growth factor beta 1. Knockdown of HGF expression attenuated EPC-induced activation of HSC apoptosis and profibrotic ability. These findings demonstrated that BM-derived EPCs could degrade ECM, promoting activated HSC apoptosis, suppressing proliferation and profibrotic ability of activated HSCs. HGF secretion by EPCs plays a key role in inducing activated HSC apoptosis and HSC profibrotic ability.

语种: 英语
所属项目编号: 30700350 ; 2005CB522902 ; 2007CB512900 ; RDK2008-06 ; 2012ZX10002003
项目资助者: National Science Foundation Fund of China ; Major State Basic Research Development Program of China (973) ; Peking University People&prime ; s Hospital Research and Development Funds ; National Science and Technology Major Project
WOS记录号: WOS:000321912000008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56070
Appears in Collections:北京大学第二临床医学院_北京大学肝病研究所_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Inst Hepatol, Beijing Key Lab Hepatitis & Immunotherapy Liver D, Beijing 100044, Peoples R China

Recommended Citation:
Liu, Feng,Liu, Zhi-da,Wu, Nan,et al. In vitro interactions between rat bone marrow-derived endothelial progenitor cells and hepatic stellate cells[J]. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL,2013,49(7):537-547.
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