Journal article
Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation
Reproduction, Fertility and Development, Vol.28(12), pp.1873-1881
2016
Abstract
The Notch and transforming growth factor (TGF)-β signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-β signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-β signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-β signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-β and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein–protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs.
Details
- Title
- Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation
- Authors/Creators
- X-F Sun (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.X-H Sun (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.S-F Cheng (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.J-J Wang (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.Y-N Feng (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.Y. Zhao (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.S. Yin (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.Z-M Hou (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.W. Shen (Author/Creator) - Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.X-F Zhang (Author/Creator) - Wuhan Polytechnic University
- Publication Details
- Reproduction, Fertility and Development, Vol.28(12), pp.1873-1881
- Publisher
- CSIRO Publishing
- Identifiers
- 991005541762607891
- Copyright
- © 2016 CSIRO
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
26 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.108 Molecular & Cell Biology - Cancer & Development
- 1.108.579 Drosophila Development
- Web Of Science research areas
- Developmental Biology
- Reproductive Biology
- Zoology
- ESI research areas
- Plant & Animal Science