TGF-ß1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway.
Reprod Biol Endocrinol
; 20(1): 22, 2022 Jan 31.
Article
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| MEDLINE
| ID: mdl-35101033
ABSTRACT
BACKGROUND:
Tightly regulation of extravillous cytotrophoblast (EVT) cell invasion is critical for the placentation and establishment of a successful pregnancy. Insufficient EVT cell invasion leads to the development of preeclampsia (PE) which is a leading cause of maternal and perinatal mortality and morbidity. Transforming growth factor-beta1 (TGF-ß1) and kisspeptin are expressed in the human placenta and have been shown to inhibit EVT cell invasion. Kisspeptin is a downstream target of TGF-ß1 in human breast cancer cells. However, whether kisspeptin is regulated by TGF-ß1 and mediates TGF-ß1-suppressed human EVT cell invasion remains unclear.METHODS:
The effect of TGF-ß1 on kisspeptin expression and the underlying mechanisms were explored by a series of in vitro experiments in a human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells. Serum levels of TGF-ß1 and kisspeptin in patients with or without PE were measured by ELISA.RESULTS:
TGF-ß1 upregulates kisspeptin expression in HTR-8/SVneo cells and primary cultures of human EVT cells. Using pharmacological inhibitor and siRNA, we demonstrate that the stimulatory effect of TGF-ß1 on kisspeptin expression is mediated via the ALK5 receptor. Treatment with TGF-ß1 activates SMAD2/3 canonical pathways as well as ERK1/2 and PI3K/AKT non-canonical pathways. However, only inhibition of ERK1/2 activation attenuates the stimulatory effect of TGF-ß1 on kisspeptin expression. In addition, siRNA-mediated knockdown of kisspeptin attenuated TGF-ß1-suppressed EVT cell invasion. Moreover, we report that serum levels of TGF-ß1 and kisspeptin are significantly upregulated in patients with PE.CONCLUSIONS:
By illustrating the potential physiological role of TGF-ß1 in the regulation of kisspeptin expression, our results may serve to improve current strategies used to treat placental diseases.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trofoblastos
/
Factor de Crecimiento Transformador beta1
/
Kisspeptinas
Límite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Reprod Biol Endocrinol
Asunto de la revista:
ENDOCRINOLOGIA
/
MEDICINA REPRODUTIVA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China