HYPOXIA INDUCIBLE FACTOR-1 ALPHA (HIF-1α) UPREGULATES AQP4 EXPRESSION IN HUMAN PLACENTAS

SZPILBARG NATALIA; DI PAOLA MAURICIO; ETCHEVERRY TOMÁS; CASTRO-PARODI MAURICIO; MARTÍNEZ NORA; FARINA MARIANA; DAMIANO, ALICIA E.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Reunión Conjunta de Sociedades de Biociencias

In preeclamptic placentas (PE), aberrations in the remodeling of the spiral arteries lead to fluctuations in O2 tension, resulting inan ischemia-reperfusion (hypoxia/reoxygenation [H/R])-type injury.Previous reports show that HIF-1α is significantly overexpressed inPE due to a proteasome dysfunction, contributing to the dysregulationof numerous genes, including syncytiotrophoblast transporterssuch as aquaporins (AQPs). In-silico analysis showed 3 putativebinding sites for HIF-1α in AQP4 promotor region. Recently, we describedthat both CoCl2 (a HIF-1α inducer) and hypoxia (H) treatmentenhanced HIF-1α and AQP4 expression in placental explants andboth returned to basal levels after reoxygenation. However, despiteHIF-1α overexpression and the proteasome dysfunction, AQP4 isdecreased in PE.Our aim is to study AQP4 expression and protein degradation pathwaysin placenta. Our hypothesis is that AQP4 mRNA expressionis increased in H and in PE via HIF-1α and that protein degradationoccurs via the lysosome pathway.This study was approved by an ethical committee. We performedAQP4 semiquantitative RT-PCR in normal and PE placental explantscultured in different O2 conditions or in the presence of CoCl2and evaluated AQP4 expression. Incubations with MG-132 or NH-4Cl, proteasome and lysosome inhibitors respectively, were also performed.We found that AQP4 mRNA increased in H, CoCl2 and PE(2.3-fold, 1.5-fold, 5-fold; n=4, p