北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第三临床医学院  > 骨科  > 期刊论文
学科主题: 临床医学
题名:
HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc
作者: Zeng, Yan; Danielson, Keith G.; Albert, Todd J.; Shapiro, Irving M.; Risbud, Makarand V.
关键词: intervertebral disc ; nucleus pulposus ; hypoxia inducible factor-1 alpha ; galectin-3 ; survival factor
刊名: JOURNAL OF BONE AND MINERAL RESEARCH
发表日期: 2007-12-01
DOI: 10.1359/JBMR.070620
卷: 22, 期:12, 页:1851-1861
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: BREAST-CARCINOMA CELLS ; NUCLEUS PULPOSUS CELLS ; EXTRACELLULAR-MATRIX ; BINDING-PROTEIN ; NOTOCHORD ; BETA-1-INTEGRINS ; DIFFERENTIATION ; FIBRONECTIN ; HYPOXIA ; ELASTIN
英文摘要:

The regulation of galectin-3 expression in skeletal tissues is not completely understood. Our studies indicate that HIF-1 alpha regulates galectin-3 expression by interacting with hypoxia regulatory elements in the promoter region. Finally, we show that galectin-3 serves a prosurvival role in the intervertebral disc.

Introduction: Earlier reports indicated that galectin-3 (gal-3) is highly expressed in the epiphyseal growth plate cartilage and the intervertebral disc. Because these skeletal tissues have a limited vascular supply and the cells reside in a low O-2 environment, we determined if the oxemic status modulates gal-3 expression.

Materials and Methods: Cells were cultured in normoxia (21% O-2) or hypoxia (2% O-2), and gal-3 expression and promoter activity were evaluated. Interaction of hypoxia inducible factor (HIF)-1 alpha with the gal-3 promoter was confirmed by gel shift and site-directed mutagenesis.

Results: There was minimal oxygen-dependent change in HIF-1 alpha levels and no change in gal-3 expression and promoter activity in nucleus pulposus cells. In contrast, hypoxia induced gal-3 mRNA, protein, and promoter activity in HeLa cells and mouse embryonic fibroblasts (MEFs) from HIF-1 alpha wildtype but not HIF-1-null mice. To evaluate the importance of HIF-1 in regulation of gal-3 expression, we overexpressed HIF-1 alpha or constitutively active-HIF-1 alpha in null MEF. An increase in gal-3 promoter activity was observed in both normoxia and hypoxia. Similarly, suppression of HIF-1 alpha in nucleus pulposus cells, and wildtype MEF, using siRNA and pharmacological inhibitors resulted in suppression of gal-3 promoter activity and mRNA levels. Analysis of the gal-3 promoter indicated that it contained two hypoxia response elements (HREs). Gel-shift and chromatin immunoprecipitation analysis confirmed that there was binding of HIF-1 alpha to the gal-3 HRE. Furthermore, site-directed mutagenesis of HRE completely blocked hypoxic induction of gal-3 promoter activity. In nucleus pulposus cells, suppression of gal-3 expression promoted FasL-mediated apoptosis.

Conclusions: Together, these studies showed that gal-3 is a HIF-1-regulated lectin that plays an important role in nucleus pulposus cell survival.

语种: 英语
WOS记录号: WOS:000251292400005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62862
Appears in Collections:北京大学第三临床医学院_骨科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA
2.Peking Univ Hosp 3, Dept Orthopaed Surg, Beijing, Peoples R China

Recommended Citation:
Zeng, Yan,Danielson, Keith G.,Albert, Todd J.,et al. HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc[J]. JOURNAL OF BONE AND MINERAL RESEARCH,2007,22(12):1851-1861.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zeng, Yan]'s Articles
[Danielson, Keith G.]'s Articles
[Albert, Todd J.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zeng, Yan]‘s Articles
[Danielson, Keith G.]‘s Articles
[Albert, Todd J.]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace