Activin A promotes human trophoblast invasion by upregulating integrin ß3 via ALK4-SMAD4 signaling.
Placenta
; 129: 62-69, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36244196
ABSTRACT
INTRODUCTION:
Activin A has been widely regarded as an important promoter of trophoblast invasion during the first trimester of pregnancy. However, whether integrin ß3 is involved in activin A-upregulated trophoblast invasion and the underlying molecular mechanisms remain largely unknown.METHODS:
We utilized immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells, as well as first-trimester chorionic villous explants as study models to investigate the function and underlying molecular mechanisms of integrin ß3 in activin A-promoted human trophoblast invasion.RESULTS:
We found that activin A increased integrin ß3 mRNA and protein levels in both HTR8/SVneo and primary EVT cells, and knockdown of integrin ß3 significantly decreased basal and activin A-upregulated trophoblast invasion. Moreover, SB431542 (a specific inhibitor of TGF-ß type Ι receptor kinase) abolished activin A-upregulated integrin ß3 expression and SMAD2/3 phosphorylation. In addition, siRNA-mediated knockdown of ALK4 or SMAD4 both abolished activin A-upregulated integrin ß3 expression in HTR8/SVneo cells, while knockdown of ALK4 or SMAD4 attenuated activin A-upregulated integrin ß3 expression in primary EVTs.DISCUSSION:
Our findings reveal the mediation role of integrin ß3 in activin A-upregulated human trophoblast invasion and that activin An upregulates integrin ß3 expression in an ALK4-SMAD4 signaling-dependent manner.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trofoblastos
/
Integrina beta3
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Placenta
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China