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.

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-1α (HIF-1α) in AQP1 modulation and we found that KD of HIF-1α 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-1α 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.

Zhang J ，Xiong Y ，Lu LX ，Wang H ，Zhang YF ，Fang F ，Song YL ，Jiang H ... -  《-》

[Effects of AQP1 overexpression on morphology and water transport in mouse Schwann cells].

Zhang J ，Yang H ，Peng L ，Jiang H ... -  《-》

Functional and transcriptional induction of aquaporin-1 gene by hypoxia; analysis of promoter and role of Hif-1α.

Abreu-Rodríguez I ，Sánchez Silva R ，Martins AP ，Soveral G ，Toledo-Aral JJ ，López-Barneo J ，Echevarría M ... -  《PLoS One》

[Study on resurrection callus culture extract on the expression and mechanism of AQP-1 in Schwann cells after injury of the resurrection].

Objective:To investigate the mechanism of AQP1 in Schwann cells and repair effect of resurrection callus culture extract on hypoxic injury cells. Method:Being cultured for 24 h, the morphological changes of the cells with different concentrations of CoCl2 were observed under the microscope and the changes of AQP1 were detected by Western blotting. Then being cultured for 24 h, the cells with different concentrations of esurrection callus culture extract were detected by CCK-8. By selecting the best concentration of resurrection callus culture extract and CoCl2, the experiment has to be continued. The changes of AQP1 and HIF-1 alpha protein were detected by Western blotting in 7 days. Result:6 μl/ml CoCl2 was selected as the optimal concentration of hypoxia model, not only because of the obvious changes in cell morphology, but no significant inhibition of cell growth, and the highest expression of AQP1. The optimum concentration of 2.5 μl/ml resurrection callus culture extract could significantly promote cell proliferation. Schwann cells increased expression of AQP1 induced expression of HIF-1 alpha, and resurrection callus culture extract can reduce AQP1 and HIF-1 alpha. Conclusion:There was a significant correlation between the expression of AQP1 and peripheral nerve Schwann cell edema, the expression of AQP1 was induced by HIF-1 after cells hypoxia. The resurrection callus culture extract can significantly decrease the expression of AQP1 and to alleviate edema in Schwann cells.

Fan YR ，Zhou HF ，Shan SJ 《-》

Localization of aquaporin-1 water channel in glial cells of the human peripheral nervous system.

The aquaporins (AQPs) are a family of water channel proteins with at least 13 mammalian members (AQPs 0-12) expressed in diverse fluid transporting tissues. AQP1, AQP4, and AQP9 have been identified in the central nervous system and demonstrated or proposed to play important roles in brain water homeostasis. Aquaporin expression in the peripheral nervous system is poorly studied. Here we report that the AQP1 water channel is specifically localized to glial cells of the peripheral nervous system by immunohistochemistry, RT-PCR, and immunoblotting. Paraffin-embedded biopsies of human pancreas, esophagus, and sciatic nerves were accessed by immunoperoxidase staining using affinity-purified AQP1, AQP4, and AQP9 antibodies. Strong AQP1 expression was identified in pancreatic nerve plexuses and in the submucosal and myenteric nerve plexuses in the esophagus. AQP1 was localized to the same cell population expressing glial fibrillary acidic protein (GFAP), but not to the neurons in the plexuses, indicating glial cell-specific expression. RT-PCR and immunoblot analysis of microdissected pancreatic ganglia confirmed the expression of AQP1 transcript and protein. Pancreatic and sciatic nerve bundles, which contain nonmyelinating and myelinating Schwann cells, respectively, were also selectively labeled by AQP1 antibody. AQP4 and AQP9, which are broadly expressed in astroglial cells in brain and spinal cord, were not localized in glial cells in the peripheral nerve plexuses. These results suggest that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in peripheral neuronal activity by regulating water homeostasis in nerve plexuses and bundles.

Gao H ，He C ，Fang X ，Hou X ，Feng X ，Yang H ，Zhao X ，Ma T ... -  《GLIA》