title: Oxygen-dependent regulation of aquaporin-3 expression.
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.
authors: Institute of Physiology, University of Duisburg-Essen, Essen, Germany; Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors: David
authors: D
authors: Hoogewijs
authors: Institute of Cardiovascular Physiology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
authors: Melanie
authors: M
authors: Vogler
authors: Institute of Cardiovascular Physiology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
authors: Eveline
authors: E
authors: Zwenger
authors: Institute of Cardiovascular Physiology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
authors: Sabine
authors: S
authors: Krull
authors: Institute of Cardiovascular Physiology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
authors: Anke
authors: A
authors: Zieseniss
keywords: hypoxia response element; hypoxia-inducible factor; oxygen; transcriptional regulation