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The Role of Annexin A1 in DNA Damage Response in Placental Cells: Impact on Gestational Diabetes Mellitus

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Autor(es):
Moreli, Jusciele Brogin ; dos Santos, Mayk Ricardo ; Paranhos Calderon, Iracema de Mattos ; Hebeda, Cristina Bichels ; Farsky, Sandra Helena Poliselli ; Bevilacqua, Estela ; Oliani, Sonia Maria
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 12, p. 15-pg., 2023-06-01.
Resumo

The functions of annexin A1 (ANXA1), which is expressed on membranes and in cytoplasmic granules, have been fully described. Nonetheless, the role of this protein in protecting against DNA damage in the nucleus is still emerging and requires further investigation. Here, we investigated the involvement of ANXA1 in the DNA damage response in placental cells. Placenta was collected from ANXA1 knockout mice (AnxA1(-/-)) and pregnant women with gestational diabetes mellitus (GDM). The placental morphology and ANXA1 expression, which are related to the modulation of cellular response markers in the presence of DNA damage, were analyzed. The total area of AnxA1(-/-) placenta was smaller due to a reduced labyrinth zone, enhanced DNA damage, and impaired base excision repair (BER) enzymes, which resulted in the induction of apoptosis in the labyrinthine and junctional layers. The placentas of pregnant women with GDM showed reduced expression of AnxA1 in the villous compartment, increased DNA damage, apoptosis, and a reduction of enzymes involved in the BER pathway. Our translational data provide valuable insights into the possible involvement of ANXA1 in the response of placental cells to oxidative DNA damage and represent an advancement in investigations into the mechanisms involved in placental biology. (AU)

Processo FAPESP: 19/19949-7 - Avaliação da atividade imunomoduladora da proteína anexina A1 em lesões cutâneas e placentárias resultantes do Diabetes Mellitus
Beneficiário:Sonia Maria Oliani
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/07328-4 - Identificação de vias endógenas para o controle da inflamação
Beneficiário:Sandra Helena Poliselli Farsky
Modalidade de apoio: Auxílio à Pesquisa - Temático