BMP6 Downregulates GDNF Expression Through SMAD1/5 and ERK1/2 Signaling Pathways in Human Granulosa-Lutein Cells

Endocrinology
Xin-Yue ZhangPeter C K Leung

Abstract

Bone morphogenetic protein (BMP) 6 is a critical regulator of follicular development that is expressed in mammalian oocytes and granulosa cells. Glial cell line‒derived 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...Continue Reading

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Citations

Jan 22, 2020·American Journal of Physiology. Endocrinology and Metabolism·Fuxin WangPeter C K Leung
Jun 12, 2020·Acta Obstetricia Et Gynecologica Scandinavica·Emily De ContoJoão Sabino Cunha-Filho
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Jan 27, 2020·Molecular and Cellular Endocrinology·Beili ChenPeter C K Leung
Aug 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiaoyan LuoYingpu Sun
Aug 12, 2021·OncoTargets and Therapy·Jiying WangCongjun Zhang

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