BMP6 Downregulates GDNF Expression Through SMAD1/5 and ERK1/2 Signaling Pathways in Human Granulosa-Lutein Cells.
Endocrinology
; 159(8): 2926-2938, 2018 08 01.
Article
de En
| MEDLINE
| ID: mdl-29750278
ABSTRACT
Bone morphogenetic protein (BMP) 6 is a critical regulator of follicular development that is expressed in mammalian oocytes and granulosa cells. Glial cell lineâderived neurotrophic factor (GDNF) is an intraovarian neurotrophic factor that plays an essential role in regulating mammalian oocyte maturation. The aim of this study was to investigate the effect of BMP6 on the regulation of GDNF expression and the potential underlying mechanisms. We used an established immortalized human granulosa cell line (SVOG cells) and primary human granulosa-lutein (hGL) cells as in vitro cell models. Our results showed that BMP6 significantly downregulated the expression of GDNF in both SVOG and primary hGL cells. With dual inhibition approaches (kinase receptor inhibitor and small interfering RNA knockdown), our results showed that both activin receptor kinase-like (ALK) 2 and ALK3 are involved in BMP6-induced downregulation of GDNF. In addition, BMP6 induced the phosphorylation of Sma- and Mad-related protein (SMAD)1/5/8 and ERK1/2 but not AKT or p38. Among three downstream mediators, both SMAD1 and SMAD5 are involved in BMP6-induced downregulation of GDNF. Moreover, concomitant knockdown of endogenous SMAD4 and inhibition of ERK1/2 activity completely reversed BMP6-induced downregulation of GDNF, indicating that both SMAD and ERK1/2 signaling pathways are required for the regulatory effect of BMP6 on GDNF expression. Our findings suggest an additional role for an intrafollicular growth factor in regulating follicular function through paracrine interactions in human granulosa cells.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Régulation de l'expression des gènes
/
Système de signalisation des MAP kinases
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Facteur neurotrophique dérivé des cellules gliales
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Protéine morphogénétique osseuse de type 6
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Cellules lutéales
Type d'étude:
Prognostic_studies
Limites:
Female
/
Humans
Langue:
En
Journal:
Endocrinology
Année:
2018
Type de document:
Article
Pays d'affiliation:
Chine