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Oxygen-dependent regulation of aquaporin-3 expression


Hoogewijs, D; Vogler, Melanie; Zwenger, Eveline; Krull, Sabine; Zieseniss, Anke (2016). Oxygen-dependent regulation of aquaporin-3 expression. Hypoxia:91-97.

Abstract

The purpose of this study was to investigate whether aquaporin-3 (AQP3) expression is altered in hypoxia and whether hypoxia-inducible transcription factor (HIF)-1 regulates the hypoxic expression. AQP3 mRNA expression was studied in L929 fibrosarcoma cells and in several tissues derived from mice that were subjected to hypoxia. Computational analysis of the AQP3 promoter revealed conserved HIF binding sites within close proximity to the translational start site, and chromatin immunoprecipitation assays confirmed binding of HIF-1α to the endogenous hypoxia response elements. Furthermore, hypoxia resulted in increased expression of AQP3 mRNA in L929 fibrosarcoma cells. Consistently, shRNA-mediated knockdown of HIF-1α greatly reduced the hypoxic induction of AQP3. In addition, mRNA analysis of organs from mice exposed to inspiratory hypoxia demonstrated pronounced hypoxia-inducible expression of AQP3 in the kidney. Overall, our findings suggest that AQP3 expression can be regulated at the transcriptional level and that AQP3 represents a novel HIF-1 target gene.
Keywords: transcriptional regulation, oxygen, hypoxia-inducible factor, hypoxia response element

Abstract

The purpose of this study was to investigate whether aquaporin-3 (AQP3) expression is altered in hypoxia and whether hypoxia-inducible transcription factor (HIF)-1 regulates the hypoxic expression. AQP3 mRNA expression was studied in L929 fibrosarcoma cells and in several tissues derived from mice that were subjected to hypoxia. Computational analysis of the AQP3 promoter revealed conserved HIF binding sites within close proximity to the translational start site, and chromatin immunoprecipitation assays confirmed binding of HIF-1α to the endogenous hypoxia response elements. Furthermore, hypoxia resulted in increased expression of AQP3 mRNA in L929 fibrosarcoma cells. Consistently, shRNA-mediated knockdown of HIF-1α greatly reduced the hypoxic induction of AQP3. In addition, mRNA analysis of organs from mice exposed to inspiratory hypoxia demonstrated pronounced hypoxia-inducible expression of AQP3 in the kidney. Overall, our findings suggest that AQP3 expression can be regulated at the transcriptional level and that AQP3 represents a novel HIF-1 target gene.
Keywords: transcriptional regulation, oxygen, hypoxia-inducible factor, hypoxia response element

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2016
Deposited On:24 Jun 2016 12:16
Last Modified:05 Aug 2017 12:06
Publisher:DovePress
ISSN:2324-1128
Funders:Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH)
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.2147/HP.S97681
Related URLs:https://www.dovepress.com/oxygen-dependent-regulation-of-aquaporin-3-expression-peer-reviewed-article-HP (Publisher)

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Licence: Creative Commons: Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)

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