Richardson S M, Knowles R, Tyler J, Mobasheri A, Hoyland J A
Tissue Injury and Repair Group, Clinical and Laboratory Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, M13 9PT, UK.
Histochem Cell Biol. 2008 Apr;129(4):503-11. doi: 10.1007/s00418-007-0372-9. Epub 2008 Jan 3.
The glucose transporters GLUT-1 and GLUT-3 are targets of the hypoxia-inducible transcription factor HIF-1alpha and it has been shown that nucleus pulposus (NP) cells in rat intervertebral discs (IVD) express both HIF-1alpha and GLUT-1. However, there is limited data on the expression of HIF-1alpha 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-1alpha; 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-1alpha mRNAs and immunohistochemistry was used to analyse protein expression and localisation of GLUTs in normal and degenerate IVD biopsies. Results confirmed HIF-1alpha, GLUT1, 3 and 9 mRNA expression in NP and AF and co-expression of each GLUT isoform with HIF-1alpha 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.
葡萄糖转运蛋白GLUT-1和GLUT-3是缺氧诱导转录因子HIF-1α的作用靶点，并且已经表明大鼠椎间盘（IVD）中的髓核（NP）细胞同时表达HIF-1α和GLUT-1。然而，关于人类IVD中HIF-1α和葡萄糖转运蛋白（GLUTs）表达的数据有限。本研究的目的是：（1）确定人类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）定位椎间盘内GLUT亚型的表达，并确定退变过程中的任何变化。采用实时PCR鉴定GLUT1、3、9和HIF-1α mRNA的表达，采用免疫组织化学分析正常和退变IVD活检组织中GLUTs的蛋白表达和定位。结果证实了NP和纤维环（AF）中HIF-1α、GLUT1、3和9 mRNA的表达，以及NP中各GLUT亚型与HIF-1α的共表达，但AF中未出现共表达。免疫组织化学显示GLUT表达存在区域差异，NP中的表达最高。GLUT表达也随着退变进展而变化。本研究表明，NP和AF细胞具有不同的GLUT表达谱，提示人类IVD代谢性质存在区域差异，并且这种环境在退变过程中发生变化。
