PMID- 23948641 OWN - NLM STAT- MEDLINE DCOM- 20140611 LR - 20211108 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 252 DP - 2013 Nov 12 TI - AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1alpha-dependent manner. PG - 68-79 LID - S0306-4522(13)00684-2 [pii] LID - 10.1016/j.neuroscience.2013.08.006 [doi] AB - Aquaporin-1 (AQP1) is the principle water channel in the peripheral nervous system (PNS) and is specifically localized to Schwann cells in the PNS. However, the pathophysiological role of AQP1 in peripheral nerves is poorly understood. Here, we utilized RNA interference by lentiviral transduction to specifically down-regulate AQP1 expression and a lentiviral overexpression protocol to up-regulate AQP1 expression, in primary Schwann cell cultures. AQP1 gene silencing resulted in a cell shrinkage phenotype, while AQP1 gene overexpression caused a cell swelling phenotype, as validated by cell volume determinations. Secondly, we utilized an in vitro hypoxia model in Schwann cells to mimic in vivo facial nerve injury. We demonstrated that AQP1 expression was induced within 8h following hypoxia injury in vitro, and that AQP1 knockdown (KD) caused the cells to resist edema following hypoxia. Finally, we investigated the hypoxic regulation of the AQP1 gene, as well as the involvement of Hypoxia-inducible factor-1alpha (HIF-1alpha) in AQP1 modulation and we found that KD of HIF-1alpha decreased hypoxia-dependent induction of endogenous AQP1 expression at both the mRNA and protein levels. Taken together, these results indicate that (1) AQP1 is an important factor responsible for the fast water transport of cultured Schwann cells and is involved in cell plasticity; (2) AQP1 alterations may be a primary factor in hypoxia-induced peripheral nerve edema; (3) HIF-1alpha participates in the hypoxic induction of the AQP1 gene; (4) AQP1 inhibition might provide a new therapeutic alternative for the treatment of some forms of peripheral nerve edema. CI - Crown Copyright (c) 2013. Published by Elsevier Ltd. All rights reserved. FAU - Zhang, J AU - Zhang J AD - Department of Plastic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Department of Plastic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. FAU - Xiong, Y AU - Xiong Y FAU - Lu, L X AU - Lu LX FAU - Wang, H AU - Wang H FAU - Zhang, Y F AU - Zhang YF FAU - Fang, F AU - Fang F FAU - Song, Y L AU - Song YL FAU - Jiang, H AU - Jiang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130812 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Aqp1 protein, mouse) RN - 0 (Hif1a protein, mouse) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 059QF0KO0R (Water) RN - 146410-94-8 (Aquaporin 1) SB - IM EIN - Neuroscience. 2014 Feb 28;260:276 MH - Animals MH - Aquaporin 1/genetics/*metabolism MH - Blotting, Western MH - Cell Hypoxia/physiology MH - Edema/genetics/metabolism MH - Fluorescent Antibody Technique MH - Gene Expression Regulation MH - Gene Knockdown Techniques MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - RNA Interference MH - Real-Time Polymerase Chain Reaction MH - Schwann Cells/cytology/*metabolism MH - Transfection MH - Up-Regulation MH - Water/*metabolism OTO - NOTNLM OT - AQP1 OT - AQP1-shRNA OT - AQP1-specific shRNA vectors OT - AQPs OT - CoCl(2) OT - GFAP OT - HIF-1alpha OT - HIFs OT - KD OT - OMG OT - PBS OT - PCR OT - PNS OT - Schwann cells OT - VEGF OT - [3H]-O-methylglucose OT - aquaporins OT - cobalt(II) chloride OT - glial fibrillary acidic protein OT - hypoxia-inducible factor-1alpha OT - hypoxia-inducible factors OT - knockdown OT - lenti-AQP1 OT - lentivirus-AQP1 OT - nerve edema OT - peripheral nerve system OT - peripheral nervous system OT - phosphate-buffered saline OT - polymerase chain reaction OT - scr-shRNA OT - scramble-shRNA vector OT - shRNA OT - short hairpin RNA OT - vascular endothelial growth factor OT - water transport EDAT- 2013/08/21 06:00 MHDA- 2014/06/12 06:00 CRDT- 2013/08/17 06:00 PHST- 2013/04/20 00:00 [received] PHST- 2013/07/05 00:00 [revised] PHST- 2013/08/03 00:00 [accepted] PHST- 2013/08/17 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/06/12 06:00 [medline] AID - S0306-4522(13)00684-2 [pii] AID - 10.1016/j.neuroscience.2013.08.006 [doi] PST - ppublish SO - Neuroscience. 2013 Nov 12;252:68-79. doi: 10.1016/j.neuroscience.2013.08.006. Epub 2013 Aug 12.