The miR-410-5p /ITGA6 axis participates in the pathogenesis of recurrent abortion by regulating the biological function of trophoblast

Wu, Shujuan; Liu, Huifan; Zhou, Mengqi; Shang, Ye; Luo, Lingbo; Chen, Jiao; Yang, Jing

doi:10.1016/j.jri.2022.103647

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…Besides, Wu et al. demonstrated that overexpression of miR-410-5p in trophoblasts inhibited the polarization of M2 macrophages ( 42 ). Chen et al.…”

Section: Discussionmentioning

confidence: 99%

Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data

et al. 2023

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Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual stromal cells (DSCs) or trophoblasts has been supposed to be the key to URSA. However, the exact molecular mechanisms in the crosstalk are not yet well understood. This study aimed to explore the potential molecule mechanism that may be involved in the communication between Mφ and DSC or trophoblast cells and determine their diagnostic characteristics by using the integrated research strategy of bioinformatics analysis, machine learning and experiments. First, microarrays of decidual tissue (GSE26787, GSE165004) and placenta tissue (GSE22490) in patients with URSA, as well as microarrays involving induced decidualization (GSE94644) and macrophage polarization in vitro (GSE30595) were derived from the gene expression omnibus (GEO) database. And 721 decidua-differentially expressed genes (DEGs), 613 placenta-DEGs, 510 Mφ polarization DEGs were obtained in URSA by differential expression analysis. Then, the protein-protein interaction (PPI) network was constructed, and the hub genes were identified by CytoHubba in Cytoscape software and validated by real-time PCR assay. Subsequently, immune enrichment analysis on decidua-DEGs and placenta-DEGs by ClueGO verified their regulation effects on Mφ. Besides, functional enrichment analysis was performed on Mφ polarization DEGs and the essential module genes derived from the weighted gene co-expression network analysis (WGCNA) to uncover the biological function that were related to abnormal polarization of Mφ. Furthermore, we screened out 29, 43 and 22 secreted protein-encoding genes from DSC-DEGs, placenta-DEGs and Mφ polarization DEGs, respectively. Besides, the hub secreted-protein-encoding genes were screened by CytoHubba. Moreover, we conducted functional enrichment analysis on these genes. And spearman correlation analysis between hub secreted-protein-encoding genes from donor cells and hub genes in recipient cells was performed to further understand the molecular mechanism of intercellular communication further. Moreover, signature genes with diagnostic value were screened from secreted protein-encoding genes by machine learning and validated by immunofluorescence co-localization analysis with clinical samples. Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained. In conclusion, this project provides new ideas for understanding the mechanism regulatory network of intercellular communication involving macrophages at the maternal-fetal interface of URSA. Also, it provides innovative insights for the diagnosis and treatment of URSA.

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“…Besides, Wu et al. demonstrated that overexpression of miR-410-5p in trophoblasts inhibited the polarization of M2 macrophages ( 42 ). Chen et al.…”

Section: Discussionmentioning

confidence: 99%

Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data

et al. 2023

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“…Protein extraction and western blotting assay were performed as described previously 27 . Total proteins were extracted from cells using RIPA lysates (Beyotime, Shanghai, China) containing protease inhibitors (MedChemExpress, NJ, USA) and phosphorylase inhibitors (MedChemExpress).…”

Section: Methodsmentioning

confidence: 99%

LncRNA AOC4P impacts the differentiation of macrophages and T‐lymphocyte by regulating the NF‐κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome

Yang,

Wu,

et al. 2023

American J Rep Immunol

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BackgroundPolycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low‐grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis.MethodsThe expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real‐time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus‐infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP‐1)‐derived macrophages and peripheral blood mononuclear cells (PBMC) were co‐cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry.ResultsDecreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co‐culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF‐κB) pathway in KGN cells.ConclusionsIn this study, we found that AOC4P regulated the NF‐κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS.

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“…Firstly, ethical and legal issues, as well as potential diseases associated with the use of these cells, may limit their applicability, similar to primary cells obtained from these tissue sources. Secondly, although the characteristics of these cells, such as ITGA6 expression ( Wu et al, 2022 ), suggest their origin from cytotrophoblast blasts, their exact location in the placenta remains unknown. Therefore, further studies are required to establish a comprehensive and systematic model.…”

Section: Cell Modelsmentioning

confidence: 99%

Exploring maternal-fetal interface with in vitro placental and trophoblastic models

Liu,

Wang,

Huang

et al. 2023

Front. Cell Dev. Biol.

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The placenta, being a temporary organ, plays a crucial role in facilitating the exchange of nutrients and gases between the mother and the fetus during pregnancy. Any abnormalities in the development of this vital organ not only lead to various pregnancy-related disorders that can result in fetal injury or death, but also have long-term effects on maternal health. In vitro models have been employed to study the physiological features and molecular regulatory mechanisms of placental development, aiming to gain a detailed understanding of the pathogenesis of pregnancy-related diseases. Among these models, trophoblast stem cell culture and organoids show great promise. In this review, we provide a comprehensive overview of the current mature trophoblast stem cell models and emerging organoid models, while also discussing other models in a systematic manner. We believe that this knowledge will be valuable in guiding further exploration of the complex maternal-fetal interface.

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The miR-410-5p /ITGA6 axis participates in the pathogenesis of recurrent abortion by regulating the biological function of trophoblast

Cited by 13 publications

References 39 publications

Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data

Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data

LncRNA AOC4P impacts the differentiation of macrophages and T‐lymphocyte by regulating the NF‐κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome

Exploring maternal-fetal interface with in vitro placental and trophoblastic models

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