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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

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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.
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