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High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration

Placentas from preeclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels 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 reduce AQP3 expression and negatively...

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Autores principales: dos Passos Junior, Rinaldo Rodrigues, de Freitas, Raiany Alves, Reppetti, Julieta, Medina, Yollyseth, Dela Justina, Vanessa, Bach, Camila Werle, Bomfim, Gisele Facholi, Lima, Victor Vitorino, Damiano, Alicia E., Giachini, Fernanda R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276056/
https://www.ncbi.nlm.nih.gov/pubmed/34267676
http://dx.doi.org/10.3389/fphys.2021.696495
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author dos Passos Junior, Rinaldo Rodrigues
de Freitas, Raiany Alves
Reppetti, Julieta
Medina, Yollyseth
Dela Justina, Vanessa
Bach, Camila Werle
Bomfim, Gisele Facholi
Lima, Victor Vitorino
Damiano, Alicia E.
Giachini, Fernanda R.
author_facet dos Passos Junior, Rinaldo Rodrigues
de Freitas, Raiany Alves
Reppetti, Julieta
Medina, Yollyseth
Dela Justina, Vanessa
Bach, Camila Werle
Bomfim, Gisele Facholi
Lima, Victor Vitorino
Damiano, Alicia E.
Giachini, Fernanda R.
author_sort dos Passos Junior, Rinaldo Rodrigues
collection PubMed
description Placentas from preeclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels 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 reduce AQP3 expression and negatively impact trophoblastic cell migration. Spontaneously hypertensive rats (SHRs) and Wistar rats (14–16 weeks) were divided into hypertensive and normotensive groups, respectively. Systolic blood pressure (SBP) was measured, and animals mated. In a third group, pregnant SHRs were treated with a TNF-α antagonist, etanercept (0.8 mg/kg, subcutaneously) on days 0, 6, 12, and 18 of pregnancy. Placentas were collected on the 20th day of pregnancy. Human placental explants, from normotensive pregnancies, were incubated with TNF-α (5, 10, and 20 ng/ml) and/or etanercept (1 μg/ml). Swan 71 cells were incubated with TNF-α (10 ng/ml) and/or etanercept (1 μg/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, and etanercept incubation reversed it. Trophoblastic cells incubated with TNF-α showed decreased cell migration and reduced AQP3 expression, and etanercept incubation ameliorated it. Altogether, these data demonstrate that high TNF-α levels negatively modulate AQP3 in placental tissue, impairing cell migration, and its relationship in a pregnancy affected by hypertension.
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spelling pubmed-82760562021-07-14 High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration dos Passos Junior, Rinaldo Rodrigues de Freitas, Raiany Alves Reppetti, Julieta Medina, Yollyseth Dela Justina, Vanessa Bach, Camila Werle Bomfim, Gisele Facholi Lima, Victor Vitorino Damiano, Alicia E. Giachini, Fernanda R. Front Physiol Physiology Placentas from preeclamptic women display augmented tumor necrosis factor-alpha (TNF-α) levels 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 reduce AQP3 expression and negatively impact trophoblastic cell migration. Spontaneously hypertensive rats (SHRs) and Wistar rats (14–16 weeks) were divided into hypertensive and normotensive groups, respectively. Systolic blood pressure (SBP) was measured, and animals mated. In a third group, pregnant SHRs were treated with a TNF-α antagonist, etanercept (0.8 mg/kg, subcutaneously) on days 0, 6, 12, and 18 of pregnancy. Placentas were collected on the 20th day of pregnancy. Human placental explants, from normotensive pregnancies, were incubated with TNF-α (5, 10, and 20 ng/ml) and/or etanercept (1 μg/ml). Swan 71 cells were incubated with TNF-α (10 ng/ml) and/or etanercept (1 μg/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, and etanercept incubation reversed it. Trophoblastic cells incubated with TNF-α showed decreased cell migration and reduced AQP3 expression, and etanercept incubation ameliorated it. Altogether, these data demonstrate that high TNF-α levels negatively modulate AQP3 in placental tissue, impairing cell migration, and its relationship in a pregnancy affected by hypertension. Frontiers Media S.A. 2021-06-29 /pmc/articles/PMC8276056/ /pubmed/34267676 http://dx.doi.org/10.3389/fphys.2021.696495 Text en Copyright © 2021 dos Passos Junior, de Freitas, Reppetti, Medina, Dela Justina, Bach, Bomfim, Lima, Damiano and Giachini. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
dos Passos Junior, Rinaldo Rodrigues
de Freitas, Raiany Alves
Reppetti, Julieta
Medina, Yollyseth
Dela Justina, Vanessa
Bach, Camila Werle
Bomfim, Gisele Facholi
Lima, Victor Vitorino
Damiano, Alicia E.
Giachini, Fernanda R.
High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title_full High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title_fullStr High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title_full_unstemmed High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title_short High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration
title_sort high levels of tumor necrosis factor-alpha reduce placental aquaporin 3 expression and impair in vitro trophoblastic cell migration
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276056/
https://www.ncbi.nlm.nih.gov/pubmed/34267676
http://dx.doi.org/10.3389/fphys.2021.696495
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