Dual role of TGF-β in early pregnancy: clues from tumor progression

Latifi, Zeinab; Nejabati, Hamid Reza; Abroon, Sina; Mihanfar, Aynaz; Farzadi, Laya; Hakimi, Parvin; Hajipour, Hamed; Nouri, Mohammad; Fattahi, Amir

doi:10.1093/biolre/ioz024

Cited by 27 publications

(26 citation statements)

References 155 publications

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“…MCP-1 attracts macrophages into the endometrium to maintain M1/M2 balance and prevent rejection of the foetus earlier in pregnancy ( 53 ). TGF-β controls apoptosis and proliferation of endometrial cells and facilitates endometrial receptivity during the peri-implantation period ( 54 ). IL-1 β, IL-6, TNF-α and IL-8 expression is increased in the myometrium and cervix during parturition ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Syncytiotrophoblast Extracellular Vesicles From Late-Onset Preeclampsia Placentae Suppress Pro-Inflammatory Immune Response in THP-1 Macrophages

et al. 2021

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Syncytiotrophoblast derived Extracellular Vesicles (STBEV) from normal pregnancy (NP) have previously been shown to interact with circulating monocytes and B cells and induce pro-inflammatory cytokine release. Early-onset preeclampsia (EOPE) is associated with an exacerbated inflammatory response, yet there is little data regarding late-onset PE (LOPE) and immune function. Here, using a macrophage/monocyte cell line THP-1, we investigated the inflammatory potential of STBEV, comprising medium/large-STBEV (>200nm) and small-STBEV (<200nm), isolated from LOPE (n=6) and normal (NP) (n=6) placentae via dual-lobe ex-vivo placental perfusion and differential centrifugation. THP-1 cells bound and internalised STBEV isolated from NP and LOPE placentae, as revealed by flow cytometry, confocal microscopy, and ELISA. STBEV-treated THP-1 cells were examined for cytokine gene expression by RT-qPCR and the cell culture media examined for secreted cytokines/chemokines. As expected, NP medium/large-STBEV significantly upregulated the transcriptional expression of TNF-α, IL-10, IL-6, IL-12, IL-8 and TGF-β compared to PE medium/large-STBEV. However, there was no significant difference in the small STBEV population between the two groups, although in general, NP small STBEVs slightly upregulated the same cytokines. In contrast, LOPE STBEV (medium and large) did not induce pro-inflammatory responses by differentiated THP-1 macrophages. This decreased effect of LOPE STBEV was echoed in cytokine/chemokine release. Our results appear to suggest that STBEV from LOPE placentae do not have a major immune-modulatory effect on macrophages. In contrast, NP STBEV caused THP-1 cells to release pro-inflammatory cytokines. Thus, syncytiotrophoblast extracellular vesicles from LOPE dampen immune functions of THP-1 macrophages, suggesting an alternative mechanism leading to the pro-inflammatory environment observed in LOPE.

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Section: Discussionmentioning

confidence: 99%

Syncytiotrophoblast Extracellular Vesicles From Late-Onset Preeclampsia Placentae Suppress Pro-Inflammatory Immune Response in THP-1 Macrophages

et al. 2021

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“…[17][18][19][20] Several factors are involved in effective implantation. [21][22][23][24][25][26][27][28] One of the most important is calcium. Certainly, Ca 2+ balance is critical in successful pregnancy.…”

Section: Introductionmentioning

confidence: 99%

S100 protein family and embryo implantation

Sadigh

Mihanfar

Fattahi

et al. 2019

J of Cellular Biochemistry

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It is well known that embryo implantation is a critical process in which embryo should be able to reach and attach to endometrium. Until now, various types of factors are involved in the regulation of this process. S100 proteins are calciumbinding proteins, which have vital roles in embryo implantation and have been considered as possible candidate markers for endometrial receptivity. However, studies regarding mode of actions of these proteins are scarce and more mechanistic insights are needed to clarify exact roles of each one of the S100 protein family. Understanding of function of these proteins in different compartments, stages, and phases of endometrium, could pave the way for conducting studies regarding the therapeutic significance of these proteins in some disorders such as recurrent implantation failure. In this review, we outlined roles and possible underlying mechanisms of S100 protein family in embryo implantation.

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“…TGF- β is a multifunctional cytokine with three isoforms (TGF- β 1, TGF- β 2, and TGF- β 3) and acts mainly through Smad pathways [ 75 ]. Evidences have proved that TGF- β plays pivotal and dual roles in the regulation of cell growth and apoptosis which is vividly described as a “switch” [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

“…During early pregnancy, the uterine cells undergo apoptosis and proliferation for the successful implantation of embryo. Those complex processes are controlled and regulated by several signal pathways, and the TGF-β signal pathway is one of them that could help to maintain normal pregnancy by balancing the proliferation and apoptosis of trophoblast cells [75]. In addition, the TGF-β signal pathway is also involved in immune and inflammatory responses by regulating indoleamine 2,3-dioxygense (IDO) expression to promote immune tolerance of the maternal-fetal interface [77], inhibiting the proliferation of human Th1 memory T cells [78].…”

Section: Tgf-β Signal Pathwaymentioning

confidence: 99%

Systems Pharmacology-Based Research on the Mechanism of Tusizi-Sangjisheng Herb Pair in the Treatment of Threatened Abortion

Yang

Luo

et al. 2020

BioMed Research International

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Threatened abortion (TA) is a common complication with high incidence in the first trimester of pregnancy, which will end in miscarriage if not treated properly. The Chinese herbs Cuscutae Semen (Tusizi in Chinese) and Herba Taxilli (Sangjisheng in Chinese) first recorded in the ancient classic medical book Shennong Bencao Jing are effective and widely used as an herb pair for the treatment of TA, while the active ingredients and the functional mechanism of Tusizi-Sangjisheng herb pair treating TA are still unknown. In order to exploit the relationship between those two herbs and TA, systems pharmacology analysis was carried out in this study. A total of 75 ingredients of Tusizi-Sangjisheng were collected from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). 12 bioactive compounds were screened, and 153 directly related targets were predicted by systematic models. Besides, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to systematically explore the potential mechanisms of Tusizi-Sangjisheng treating TA. Meanwhile, Compound-Target (C-T), Target-Disease (T-D), and Target-Pathway (T-P) networks were constructed to further quest the underlying functional mechanisms of Tusizi-Sangjisheng. As a result, 31 targets and 3 key pathways were found to be directly related to TA that includes mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt), and transforming growth factor-β (TGF-β) signaling pathways. The results in this study may provide some valuable clues about the molecular mechanisms of the efficient Chinese herb pair Tusizi-Sangjisheng in the treatment of TA.

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Dual role of TGF-β in early pregnancy: clues from tumor progression

Cited by 27 publications

References 155 publications

Syncytiotrophoblast Extracellular Vesicles From Late-Onset Preeclampsia Placentae Suppress Pro-Inflammatory Immune Response in THP-1 Macrophages

Syncytiotrophoblast Extracellular Vesicles From Late-Onset Preeclampsia Placentae Suppress Pro-Inflammatory Immune Response in THP-1 Macrophages

S100 protein family and embryo implantation

Systems Pharmacology-Based Research on the Mechanism of Tusizi-Sangjisheng Herb Pair in the Treatment of Threatened Abortion

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