ArticleCell death & disease2020
SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Acute Heat Stress Remodels Mitochondrial Ultrastructure and Time-Dependent Transcriptomic Landscapes in Bovine Granulosa Cells.Animals : an open access journal from MDPI · 2026Article
- Protective effects of ginseng against reproductive injury: mechanisms and research progress.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Frizzled-4 promotes bone formation in chickens via activation of the canonical Wnt signaling pathway.Poultry science · 2026Article
- Review
- Association of SMAD4 gene polymorphisms with human papillomavirus infection and risk of cervical cancer: a case-control study.BMC cancer · 2026Article
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Integrative Transcriptome Analysis Across Follicles Highlights Key Regulatory Pathways in Low and High-Egg-Laying Hens.Animals : an open access journal from MDPI · 2025Article
- Integrated Whole-Transcriptome Analysis to Elucidate the Core Regulatory Network of circRNA Involved in Ovarian Development and Reproductive Capacity Differences in Sheep: circRNA2058-miR-9226-5p-Animals : an open access journal from MDPI · 2025Article
- Article
- Transcriptomic signatures and network-based methods uncover new senescent cell anti-apoptotic pathways and senolytics.The FEBS journal · 2025Article
- TGF-β1 Mediates Novel-m0297-5p TargetingInternational journal of molecular sciences · 2025Article
- Mechanisms of follicular atresia: focus on apoptosis, autophagy, and ferroptosis.Frontiers in endocrinology · 2025Review
- miR-184, a downregulated ovary-elevated miRNA transcriptionally activated by SREBF2, exerts anti-apoptotic properties in ovarian granulosa cells through inducing SMAD3 expression.Cell death & disease · 2024Article
- Oxidative stress controls lncRNA-mediated sow granulosa cell functions in a FoxO1-dependent manner.Journal of animal science and biotechnology · 2024Article
- Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway.Respiratory research · 2024Article
- Functional Study of PTSMAD4 in the Spermatogenesis of the Swimming CrabInternational journal of molecular sciences · 2024Article
- ZEB2 reduction contributes to pre-eclampsia via Wnt/β-Catenin pathway.Cell division · 2024Article
- Synergistic cooperation between the β-catenin and SF1 regulates progesterone synthesis in laying hen ovarian granulosa cells.Animal biotechnology · 2024Article
- In pre-clinical study fetal hypoxia caused autophagy and mitochondrial impairment in ovary granulosa cells mitigated by melatonin supplement.Journal of advanced research · 2024Article
- The possible regulatory role of miR-4463 and its target geneInternational journal of reproductive biomedicine · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TGF-β and Wnt signaling pathways are interrelated in many cell types and tissues, and control cell functions in coordination. Here, we report that SMAD4, a downstream effector of the TGF-β signaling pathway, induces FZD4, a receptor of the Wnt signaling pathway, establishing a novel route of communication between these two pathways in granulosa cells (GCs). We found that SMAD4 is a strong inducer of FZD4, not only initiating FZD4 transcription but also activating FZD4-dependent Wnt signaling and GC apoptosis. Furthermore, we identified the direct and indirect mechanisms by which SMAD4 promotes expression of FZD4 in GCs. First, SMAD4 functions as a transcription factor to directly bind to the FZD4 promoter region to increase its transcriptional activity. Second, SMAD4 promotes production of SDNOR, a novel lncRNA that acts as a sponge for miR-29c, providing another mean to block miR-29c from degenerating FZD4 mRNA. Overall, our findings not only reveal a new channel of crosstalk between the TGF-β and Wnt signaling pathways, SMAD4-FZD4 axis, but also provide new insights into the regulatory network of GC apoptosis and follicular atresia. These RNA molecules, such as miR-29c and lnc-SDNOR, represent potential targets for treatment of reproductive diseases and improvement of female fertility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.