TGF-β induces Smad2 Phosphorylation, ARE Induction, and Trophoblast Differentiation
- Author:
Renee E ALBERS
1
;
Kaisa SELESNIEMI
;
David R C NATALE
;
Thomas L BROWN
Author Information
- Publication Type:Original Article
- Keywords: Placenta; Labyrinthine; TGF-β; Differentiation; Smad
- MeSH: Activins; Animals; Blotting, Western; Cell Death; Luciferases; Mice; Microscopy; Phosphorylation; Placenta; Protein Isoforms; Response Elements; Signal Transduction; Stem Cells; Transcriptional Activation; Transforming Growth Factor beta; Trophoblasts
- From:International Journal of Stem Cells 2018;11(1):111-120
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. MATERIALS AND METHODS: In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. RESULTS AND CONCLUSIONS: In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.
