Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1α in normal and degenerate human intervertebral disc
Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1α in normal and degenerate human intervertebral disc
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DOI：
10.1007/s00418-007-0372-9
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发表时间：
2008-04-01
影响因子：
2.3
通讯作者：
Hoyland, J. A.
中科院分区：
文献类型：
--
作者：
Richardson, S. M.;Knowles, R.;Hoyland, J. A.
葡萄糖转运蛋白GLUT-1和GLUT-3是低氧诱导转录因子HIF-1α的靶标，已有研究表明大鼠髓核细胞同时表达HIF-1α和GLUT-1。然而，有关HIF-1α和GLUTS在人类IVD中表达的数据有限。其目的是(1)确定人IVD细胞是否像关节软骨细胞一样表达GLUT-1、3和9，以及是否与HIF-1α共表达；(2)定位GLUT异构体在椎间盘中的表达，并确定退变过程中的任何变化。实时定量聚合酶链式反应检测GLUT1、GLU3、GLU9和HIF-1αmRNAs的表达，免疫组织化学方法检测GLUT1、3、9和HIF-1α在正常和退行性IVD组织中的表达和定位。结果证实HIF-1α、GLUT1、3和9mRNA在NP和AF中均有表达，并且各GLUT亚型在NP中与HIF-1α共表达，但在AF中不表达。免疫组织化学显示GLUT的表达存在区域差异，以NP表达最高。随着退变的进展，Glut的表达也发生了变化。这项研究表明，NP和AF细胞具有不同的Glut表达谱，这表明人类IVD的代谢性质存在区域差异，这种环境在退变过程中会发生变化。
\ The glucose transporters GLUT-1 and GLUT-3 are targets of the hypoxia-inducible transcription factor HIF-1 alpha and it has been shown that nucleus pulposus (NP) cells in rat intervertebral discs (IVD) express both HIF-1 alpha and GLUT-1. However, there is limited data on the expression of HIF-1 alpha and GLUTs in human IVD. The aim here was to (1) determine whether, like articular chondrocytes, human IVD cells express GLUT-1, 3 and 9 and whether there was any co-expression with HIF-1 alpha; and (2) to localise expression of the GLUT isoforms in the disc and identify any changes during degeneration. Real-time PCR was used to identify expression of GLUT1, 3, 9 and HIF-1 alpha mRNAs and immunohistochemistry was used to analyse protein expression and localisation of GLUTs in normal and degenerate IVD biopsies. Results confirmed HIF-1 alpha, GLUT1, 3 and 9 mRNA expression in NP and AF and co-expression of each GLUT isoform with HIF-1 alpha in the NP, but not the AF. Immunohistochemistry demonstrated regional differences in GLUT expression, with the highest expression being in the NP. GLUT expression also changed as degeneration progressed. This study demonstrates that NP and AF cells have different GLUT expression profiles that suggest regional differences in the metabolic nature of the human IVD and that this environment changes during degeneration.