ArticleReproductive biology and endocrinology : RB&E2022
TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway.
Article in Reproductive biology and endocrinology : RB&E, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
- The KISS1/KISS1R Axis in Human Placentation: Molecular Mechanisms and Implications for Foetal Growth Restriction and Pre-Eclampsia.International journal of molecular sciences · 2026Review
- JEG-3 Trophoblast Cells Influence ILC-like Transformation of NK Cells In Vitro.International journal of molecular sciences · 2025Article
- Gaps in maternal-fetal interface rejection response: chronic histiocytic intervillositis.Frontiers in immunology · 2025Review
- Article
- Understanding the intersection between placental development and cancer: Lessons from the tumor suppressor BAP1.Communications biology · 2024Review
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- Association between single nucleotide polymorphisms, TGF-β1 promoter methylation, and polycystic ovary syndrome.BMC pregnancy and childbirth · 2024Article
- Bioinformatics-based Identification of Ferroptosis-related Genes and their Diagnostic Value in Gestational Diabetes Mellitus.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Mendelian randomization supports genetic liability to hospitalization for COVID-19 as a risk factor of pre-eclampsia.Frontiers in cardiovascular medicine · 2024Article
- The Role of TGF-β during Pregnancy and Pregnancy Complications.International journal of molecular sciences · 2023Review
- Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer.Exploration of targeted anti-tumor therapy · 2023Review
- Decidual cells and decidualization in the carnivoran endotheliochorial placenta.Frontiers in cell and developmental biology · 2023Review
- The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses.International journal of molecular sciences · 2022Review
- The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review.International journal of molecular sciences · 2022Review
- Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model.Frontiers in endocrinology · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTightly regulation of extravillous cytotrophoblast (EVT) cell invasion is critical for the placentation and establishment of a successful pregnancy. Insufficient EVT cell invasion leads to the development of preeclampsia (PE) which is a leading cause of maternal and perinatal mortality and morbidity. Transforming growth factor-beta1 (TGF-β1) and kisspeptin are expressed in the human placenta and have been shown to inhibit EVT cell invasion. Kisspeptin is a downstream target of TGF-β1 in human breast cancer cells. However, whether kisspeptin is regulated by TGF-β1 and mediates TGF-β1-suppressed human EVT cell invasion remains unclear.
methodsThe effect of TGF-β1 on kisspeptin expression and the underlying mechanisms were explored by a series of in vitro experiments in a human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells. Serum levels of TGF-β1 and kisspeptin in patients with or without PE were measured by ELISA.
resultsTGF-β1 upregulates kisspeptin expression in HTR-8/SVneo cells and primary cultures of human EVT cells. Using pharmacological inhibitor and siRNA, we demonstrate that the stimulatory effect of TGF-β1 on kisspeptin expression is mediated via the ALK5 receptor. Treatment with TGF-β1 activates SMAD2/3 canonical pathways as well as ERK1/2 and PI3K/AKT non-canonical pathways. However, only inhibition of ERK1/2 activation attenuates the stimulatory effect of TGF-β1 on kisspeptin expression. In addition, siRNA-mediated knockdown of kisspeptin attenuated TGF-β1-suppressed EVT cell invasion. Moreover, we report that serum levels of TGF-β1 and kisspeptin are significantly upregulated in patients with PE.
conclusionsBy illustrating the potential physiological role of TGF-β1 in the regulation of kisspeptin expression, our results may serve to improve current strategies used to treat placental diseases.
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