Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Le Maitre, CL
Conner, Matthew T.
MetadataShow full item record
AbstractObjectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes.
CitationJohnson, Z. I., Gogate, S. S., Day, R., Binch, A., Dessislava Z. M., Chiverton, N., Cole, A., Conner, M., Shapiro, I. M., Le Maitre, C. L. and Risbud, M. V. (2015) Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells, Oncotarget, 6(14), pp. 11945-11958.
SponsorsThis work is supported by grants from the National Institutes of Health AR055655, AR064733 and AR050087 (MVR). Zariel I. Johnson is supported by T32 AR052273.
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International
- HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc.
- Authors: Zeng Y, Danielson KG, Albert TJ, Shapiro IM, Risbud MV
- Issue date: 2007 Dec
- PHD/HIF-1 upregulates CA12 to protect against degenerative disc disease: a human sample, in vitro and ex vivo study.
- Authors: Chen S, Fang XQ, Wang Q, Wang SW, Hu ZJ, Zhou ZJ, Xu WB, Wang JY, Qin A, Fan SW
- Issue date: 2016 May
- AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1α-dependent manner.
- Authors: Zhang J, Xiong Y, Lu LX, Wang H, Zhang YF, Fang F, Song YL, Jiang H
- Issue date: 2013 Nov 12
- Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc.
- Authors: Skubutyte R, Markova D, Freeman TA, Anderson DG, Dion AS, Williams CJ, Shapiro IM, Risbud MV
- Issue date: 2010 Sep
- SIRT1 expression is refractory to hypoxia and inflammatory cytokines in nucleus pulposus cells: Novel regulation by HIF-1α and NF-κB signaling.
- Authors: Wang X, Li H, Xu K, Zhu H, Peng Y, Liang A, Li C, Huang D, Ye W
- Issue date: 2016 Jun