Cyclophilin A inhibits trophoblast migration and invasion in vitro and vivo through p38/ERK/JNK pathways and causes features of preeclampsia in mice.
Life Sci
; 261: 118351, 2020 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-32858039
ABSTRACT
AIMS:
Numerous studies suggest that excessive maternal inflammation and defective extravillous trophoblast (EVT) invasion could contribute to the development of preeclampsia (PE), but the underlying mechanism remains unclear. Some evidence suggests that CyPA is elevated in PE. This research aims to investigate the effect of recombinant human CyPA on trophoblast migration and invasion both in vitro and in vivo. MATERIALS ANDMETHODS:
We detected the expression and localization of CyPA in human placenta and explored the effects of CyPA on cell migration and invasion on HTR8/SVneo cell. Additionally, the expression levels of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway were detected. We established a mouse model by injecting pregnant mice with recombinant human CyPA and measured blood pressure, albumin/creatinine ratio, fetal and placenta weight of mice. Moreover, we examined the placental histology and MMP-2/9 and p38/ERK/JNK expression. KEYFINDINGS:
Our results showed that CyPA inhibited the migration and invasion of HTR8/SVneo cells in a dose-dependent manner, decreasing the expression of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway. Silencing CyPA could reverse the above effects. Moreover, CyPA could induce PE-like features in pregnant mice and disrupt the structure of the mouse placenta by reducing the junctional zone area. CyPA attenuated the trophoblast invasiveness in mice placenta by downregulating MMP-2/9 expression and p38/ERK/JNK pathway activity.SIGNIFICANCE:
We proposed that CyPA could inhibit trophoblast migration and invasion both in vitro and in vivo, which was involved in PE development.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Preeclampsia
/
Trofoblastos
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Movimiento Celular
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Sistema de Señalización de MAP Quinasas
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Ciclofilina A
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
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Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Life Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
China