Fator de necrose tumoral-alfa modula a migração celular trofoblástica via diminuição da expressão de aquaporina 3 em tecido placentário

Abstract

Placentas from pre-eclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels simultaneously with reduced expression of aquaporin 3 (AQP3). However, whether TNF- α modulates AQP3 expression remains to be elucidated. We hypothesize that elevated levels of

TNF-α, observed during hypertensive pregnancy, reduces AQP3 expression and negatively impact on trophoblastic cell migration. Spontaneously hypertensive rats (SHR) and Wistar (12- 14 wk) were divided into hypertensive and normotensive groups, respectively. In a third group, SHRs were treated with a TNF-α antagonist, etanercept (0.8 mg/kg, i.p.). Systolic blood pressure (SBP) was measured, and animals mated. Placentas were collected at 21 days of pregnancy. TNF-α (0, 5, 10 and 20 ng/mL,16 hours) was incubated with human placental explants, from normotensive pregnancies. Swan 71 cells were incubated with TNF-α (10 ng/mL) and subjected to the wound healing assay. AQP3 expression was assessed by western blot and TNF-α levels by ELISA. SBP (mmHg) was elevated in the hypertensive group, and etanercept treatment reduced this parameter. Placental TNF-α levels (pg/mL) were higher in the hypertensive group. AQP3 expression was reduced in the hypertensive group, and etanercept treatment reversed this parameter. Explants submitted to TNF-α exposition displayed reduced expression of AQP3. Trophoblastic cells incubated with TNF-α showed decreased cell migration and reduced AQP3 expression. Altogether, these data demonstrate that TNF-α negatively modulates AQP3 in placental tissue, impacting cell migration, and its relationship in a pregnancy affected by hypertensive conditions.