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. 2020 Oct 28;8:573781. doi: 10.3389/fcell.2020.573781

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Copyright © 2020 Xie, Zhu, Chang, Klausen, Dong and Leung.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed model of the stimulatory effect of growth differentiation factor 8 (GDF8) on relative transwell cells in human trophoblast cells. GDF8 binds to a heterotetrameric receptor complex comprised of type I (ALK5) and type II receptors. Ligand-induced activation of the receptor complex results in the phosphorylation and activation of ALK5, leading to the activation of receptor-regulated SMAD2 and SMAD3. Phosphorylated SMAD2 and SMAD3 form a heterotrimeric complex with common SMAD4 that translocates into the nucleus where it binds the FSTL3 promoter and stimulates the transcription and secretion of FSTL3, which in turn promotes cell invasion of human trophoblast cells.