Activin A increases human trophoblast invasion by upregulating integrin ß1 through ALK4.
FASEB J
; 35(2): e21220, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33230889
ABSTRACT
Activin A promotes human trophoblast invasion during the first trimester of pregnancy and is associated with preeclampsia and pregnancy-induced hypertension (PE/PIH) in naturally conceived pregnancies. However, whether integrin ß1 mediates activin A-increased trophoblast invasion remains unknown and the evidence is limited regarding the predictive value of activin A for PE/PIH in women receiving in vitro fertilization (IVF) treatment. Here, we studied the role and underlying molecular mechanisms of integrin ß1 in activin A-promoted invasion in immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells. A nest case-control study was designed to investigate the predictive/diagnostic value of activin A in IVF pregnancies. Results showed that integrin ß1 expression increased after activin A treatment and knockdown of integrin ß1 significantly decreased both basal and activin A-increased HTR8/SVneo cell invasion. SB431542 (TGF-ß type I receptors inhibitor) abolished activin A-induced SMAD2/SMAD3 phosphorylation and integrin ß1 overexpression. Activin A-upregulated integrin ß1 expression was attenuated after the depletion of ALK4 or SMAD4 in both HTR8/SVneo and primary EVT cells. Furthermore, we found similar first-trimester activin A levels in IVF patients with or without subsequent PE/PIH. These results reveal that integrin ß1 mediates activin A-promoted trophoblast invasion through ALK4-activated SMAD2/3-SMAD4 pathway, and the predictive/diagnostic value of first-trimester maternal serum activin A for hypertensive disorders of pregnancy might be different in IVF population.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trofoblastos
/
Movimento Celular
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Integrina beta1
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Ativinas
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Receptores de Ativinas Tipo I
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article