Laboratorio de Biología de la Reproducción, Cátedra de Biología Celular y Molecular, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Placenta. 2011 Dec;32(12):1050-6. doi: 10.1016/j.placenta.2011.09.022. Epub 2011 Oct 21.
The AQP9 gene contains a negative insulin response element, suggesting that it may be modulated by insulin. Previously, we reported AQP9 overexpression in preeclamptic placentas but a lack of functionality of AQP9 in water and mannitol transport. We also observed high serum levels of insulin and TNF-α in preeclamptic women.
To evaluate whether AQP9 expression is regulated by insulin in the human placenta, and whether the dysregulation of AQP9 observed in preeclamptic placentas may be related to the inability to respond to insulin stimuli.
Explants from normal and preeclamptic placentas were cultured at different concentrations of insulin. Treatment with TNF-α was used to induce phosphorylation of insulin receptor substrate (IRS), which may desensitize insulin action. AQP9 molecular expression and water uptake was determined.
Insulin decreased the molecular expression of AQP9 exclusively in explants from normal placentas in a concentration-dependent manner. Treatment with TNF-α previous to insulin addition prevented these changes. Moreover, insulin treatment did not modify water uptake neither its sensitivity to HgCl(2.)
AQP9 water permeability seems to be independent of its molecular expression, strongly suggesting that AQP9 might not have a key role in water transport in human placenta. We also propose another mechanism of down-regulation of AQP9 molecular expression mediated by insulin in a concentration-dependent manner in human placenta and provide new evidence that in preeclamptic placentas the mechanisms of insulin signaling may be altered, producing an overexpression of AQP9 that does not correlate with an increase in its functionality.
AQP9 基因含有一个负胰岛素反应元件，提示其可能受胰岛素调节。此前，我们曾报道过子痫前期胎盘 AQP9 过表达，但 AQP9 在水和甘露醇转运方面缺乏功能。我们还观察到子痫前期妇女血清中胰岛素和 TNF-α 水平升高。
评估 AQP9 在人胎盘是否受胰岛素调节，以及子痫前期胎盘中观察到的 AQP9 失调是否与不能对胰岛素刺激作出反应有关。
正常和子痫前期胎盘的组织培养物在不同浓度的胰岛素下培养。用 TNF-α 处理以诱导胰岛素受体底物（IRS）的磷酸化，这可能使胰岛素作用脱敏。测定 AQP9 分子表达和水摄取。
胰岛素以浓度依赖的方式特异性地下调正常胎盘组织培养物中 AQP9 的分子表达。在加入胰岛素之前用 TNF-α 处理可预防这些变化。此外，胰岛素处理不会改变水摄取及其对 HgCl2 的敏感性。
AQP9 水通透性似乎与其分子表达无关，这强烈表明 AQP9 可能不是人胎盘水转运的关键。我们还提出了另一种机制，即胰岛素以浓度依赖的方式下调人胎盘 AQP9 的分子表达，并且提供了新的证据表明，在子痫前期胎盘中，胰岛素信号转导的机制可能发生改变，导致 AQP9 的过度表达，但与其功能的增加无关。
