ArticlePloS one2013
Soluble human leukocyte antigen-g5 activates extracellular signal-regulated protein kinase signaling and stimulates trophoblast invasion.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Endometrial Assembloid Model Reveals Endometrial Gland Development Regulation by Estradiol-Driven WNT7B Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Maternal causation of early-onset pre-eclampsia: excessive endometrial gland-derived apolipoprotein D induces placental ferroptosis and developmental abnormalities.Journal of biomedical science · 2025Article
- Mechanism of microRNA-152 Regulating Decidual Natural Killer Cell Viability and Affecting Trophoblast Cell Invasiveness via the HLA-G/KIR2DL4 Axis.The Kaohsiung journal of medical sciences · 2025Article
- Immune Evasion Through Human Leukocyte Antigen Implications and Its Impact on Targeted Therapy.Cureus · 2024Review
- Application of a JEG-3 organoid model to study HLA-G function in the trophoblast.Frontiers in immunology · 2023Article
- Human Leukocyte Antigens in Pregnancy and Preeclampsia.Frontiers in genetics · 2022Review
- Histocompatibility Antigen, Class I, G (HLA-G)'s Role during Pregnancy and Parturition: A Systematic Review of the Literature.Life (Basel, Switzerland) · 2021Review
- HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance.Frontiers in immunology · 2021Review
- HLA-G Expression in Tumor Tissues and Soluble HLA-G Plasma Levels in Patients with Gastrointestinal CancerAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Clinical Significance of Potential Unidentified HLA-G Isoforms Without α1 Domain but Containing Intron 4 in Colorectal Cancer Patients.Frontiers in oncology · 2018Article
- KIR, LILRB and their Ligands' Genes as Potential Biomarkers in Recurrent Implantation Failure.Archivum immunologiae et therapiae experimentalis · 2017Review
- Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage.Archivum immunologiae et therapiae experimentalis · 2016Article
- Co-expression of ILT4/HLA-G in human non-small cell lung cancer correlates with poor prognosis and ILT4-HLA-G interaction activates ERK signaling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy.Molecular medicine (Cambridge, Mass.) · 2015Article
- HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche.Frontiers in immunology · 2015Review
- The many faces of human leukocyte antigen-G: relevance to the fate of pregnancy.Journal of immunology research · 2014Review
- HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble human leukocyte antigen-G (HLA-G) is a non-classical class Ib HLA molecule that is secreted from blastocysts. Soluble HLA-G modulates the immune tolerance of the mother and can be used as a prognostic factor for the clinical pregnancy rate. However, the underlying mechanism of how soluble HLA-G5 affects pregnancy remains largely unknown. We hypothesized that soluble HLA-G5 promotes successful implantation and pregnancy by modulating trophoblast invasion through receptor binding and activation of extracellular signal-regulated protein kinase (ERK) signaling pathway. Recombinant HLA-G5 protein over-expressed in E. coli BL21 was purified to near homogeneity. We studied the expression of HLA-G5 and its receptors, the leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) and killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), in primary trophoblasts and trophoblastic (JAr and JEG-3) cell lines by florescence-labeled HLA-G5. HLA-G5 was detected in the primary trophoblasts and JEG-3 cells. The LILRB1 and KIR2DL4 receptors were expressed in both primary trophoblasts and trophoblastic cell lines. HLA-G5 stimulated cell invasion (p<0.05) and increased urokinase (uPA) and matrix metalloproteinases (MMPs) transcripts and their activity (p<0.05) in trophoblastic cells. HLA-G5 activated the ERK signaling pathway and induced ERK1/2 phosphorylation in the trophoblastic cell lines. Addition of ERK inhibitors (U0126 and PD98059) nullified the stimulatory effect of HLA-G5 on trophoblastic cell invasion. Taken together, HLA-G5 induced trophoblast invasion by binding to KIR2DL4 and LILRB1, by increasing uPA and MMPs expressions and by activating the ERK signaling pathway.
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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.