Matrix metalloproteinases improves trophoblast invasion and pregnancy potential in mice

Zhang, Shimin; Mesalam, Ayman; Joo, Myeong-Dong; Lee, Kyeong-Lim; Hwang, Ji-Yoon; Xu, Lianguang; Song, Seok-Hwan; Koh, Phil-Ok; Yuan, Yawei; Lv, Wenfa; Kong, Il‐Keun

doi:10.1016/j.theriogenology.2020.02.002

Cited by 23 publications

(14 citation statements)

References 35 publications

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“…MMPs secreted by trophoblast cells are critical for their migration and invasion ability and successful embryo implantation [ 24 , 25 ]. MMP2 has been implicated in the remodelling of the ECM to assist trophoblast cell invasion, and a previous study showed that enhancing MMP-2/9 activity could promote trophoblast cell invasion and migration [ 26 ]. Remarkably, Fyn was reported to facilitate cell invasion and migration by regulating MMP2 and MMP9 [ 27 , 28 ], which was in line with our results.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Liu

Ding

Xie

2022

BioMed Research International

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Fyn has been proven to be involved in various cell behaviors and pathophysiological processes. However, the expression and roles of Fyn in trophoblasts remain unclear. Here, we aimed to evaluate the participation of Fyn in trophoblast behavior and function, and the related mechanisms were briefly explored. Fyn expression in the HTR-8/SVneo, JEG-3, and JAR cell lines was evaluated by immunofluorescence, quantitative real-time PCR and western blotting. Fyn expression in human hydatidiform moles was also determined by immunohistochemistry and western blot. To explore the effects of Fyn, HTR-8/SVneo and JEG-3 cells were transfected with Fyn shRNA or overexpression plasmid or treated with the Fyn activity inhibitor SU6656 or ERK1/2 inhibitor U0126. The migration, proliferation, and apoptosis of trophoblast cells were assessed using transwell assays, flow cytometry, and cell counting kit-8 assays, respectively. The production of primary inflammatory cytokines, HLA-G and active matrix metallopeptidase (MMP) 2/9, and the phosphorylation of ERK1/2 and STAT3 were evaluated by ELISA, western blot, or gelatin zymography. The results showed that Fyn was expressed by trophoblast cells, mainly in the cytoplasm and membrane. Fyn expression and activity levels both increased in order from HTR-8/SVneo and JAR to JEG-3. The overexpression of Fyn promoted the proliferation and migration of trophoblast cells and inhibited their apoptosis, while the opposite effects were observed for Fyn knockdown and inhibition. Fyn regulated inflammatory cytokine production in trophoblast cells by promoting TGF-β and IL-4 secretion while inhibiting IFN-γ and TNF-α secretion. Moreover, HLA-G expression in JEG-3 was positively regulated by Fyn. Fyn also facilitated the expression of active MMP2/9 and the activation of ERK1/2 and STAT3. Besides, it was confirmed that Fyn regulated trophoblast cell activities through ERK1/2 signal pathway by using U0126. Our study first detected the expression of Fyn in trophoblast cells. Fyn played pivotal roles in trophoblast cell behaviors and function, ERK1/2 was one of its targets, and MMP2/9 and STAT3 may also be involved in the regulatory mechanism.

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Section: Discussionmentioning

confidence: 99%

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Liu

Ding

Xie

2022

BioMed Research International

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“…MMP-9 is secreted by tumor cells and various immune cells in the stroma. The products formed by MMP-9 activation can decompose the majority of substances present in the basement membrane and extracellular matrix ( 27 ). In addition, angiogenesis is increased by the presence of VEGF in tumors ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of hematopoietic progenitor cells on the biological characteristics of colon cancer tumor stem cells

Guan¹,

Yang²,

Wu³

2021

Transl Cancer Res TCR

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Background Cancer stem cells (CSCs) are a type of tumor cell that are self-sustaining and can differentiate into several different types of cells. The present study aims to investigate the effect of hematopoietic progenitor cells (HPCs) on the biological behavior of colon CSCs (CCSCs) and to determine the underlying molecular mechanisms of liver metastasis in colorectal cancer. Methods Subsets of CCSCs were isolated from stem-like HCT116 cells and cocultured with CD133 + HPCs in vitro. Colony formation assay, and CCK-8 were used to assess the effects of HPCs on CCSC subsets. Invasive and migration assay were done to study the effects of HPCs mediated metastatic capacity of CCSC subsets. Expression of MMP-9, VEGF, E-cadherin and β-catenin was analyzed by qPCR and Western blotting. Results CCK-8 and colony formation assays showed that HPCs significantly promoted proliferation and colony formation of the CCSC subsets (P=0.031). HPCs also significantly enhanced the migration (P=0.011) and invasive capacity (P=0.001) of the CCSC subsets. Quantitative PCR showed that MMP-9 and VEGF expression in CCSC subsets were significantly upregulated (P=0.000 and P=0.005). Western blotting showed that MMP-9, VEGF and β-catenin expression in CCSC subsets were significantly upregulated (P=0.000, P=0.005, P=0.000). The protein expression levels of E-cadherin in the CCSC subsets was significantly downregulated (P=0.002). Conclusions CD133 + HPCs enhanced migration, invasion and proliferation of CCSC subsets in vitro .

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“…By contrast, the expression of other genes strongly implicated in endometrial receptivity and adhesive capacity including CASP4 [ 37 ] , MMP2 [ 38 ] , SGK1 [ 39 ] , ARF6 [ 40 ] , CD44 [ 41 ] , CDH1 [ 42 ] , CDH2 [ 42 ], and MDM2 remained unchanged in TPP1 siRNA-transfected Ishikawa cells, suggesting TPP1 does not act via these molecules in exerting its effects on epithelial cells and receptivity associated adhesive capacity.…”

Section: Discussionmentioning

confidence: 99%

Tripeptidyl peptidase I promotes human endometrial epithelial cell adhesive capacity implying a role in receptivity

Santos

Ling

Dimitriadis

2020

Reprod Biol Endocrinol

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The endometrium undergoes cyclic remodelling throughout the menstrual cycle in preparation for embryo implantation which occurs in a short window during the mid-secretory phase. It is during this short ‘receptive window’ that the endometrial luminal epithelium acquires adhesive capacity permitting blastocysts firm adhesion to the endometrium to establish pregnancy. Dysregulation in any of these steps can compromise embryo implantation resulting in implantation failure and infertility. Many factors contribute to these processes including TGF-β, LIF, IL-11 and proteases. Tripeptidyl peptidase 1 (TPP1) is a is a lysosomal serine-type protease however the contribution of the TPP1 to receptivity is unknown. We aimed to investigate the role of TPP1 in receptivity in humans.In the current study, TPP1 was expressed in both epithelial and stromal compartments of the endometrium across the menstrual cycle. Expression was confined to the cytoplasm of luminal and glandular epithelial cells and stromal cells. Staining of mid-secretory endometrial tissues of women with normal fertility and primary unexplained infertility showed reduced immunostaining intensity of TPP1 in luminal epithelial cells of infertile tissues compared to fertile tissues. By contrast, TPP1 levels in glandular epithelial and stromal cells were comparable in both groups in the mid-secretory phase. Inhibition of TPP1 using siRNA compromised HTR8/SVneo (trophoblast cell line) spheroid adhesion on siRNA-transfected Ishikawa cells (endometrial epithelial cell line) in vitro. This impairment was associated with decreased sirtuin 1 (SIRT1), BCL2 and p53 mRNA and unaltered, CD44, CDH1, CDH2, ITGB3, VEGF A, OSTEOPONTIN, MDM2, CASP4, MCL1, MMP2, ARF6, SGK1, HOXA-10, LIF, and LIF receptor gene expression between treatment groups. siRNA knockdown of TPP1 in primary human endometrial stromal cells did not affect decidualization nor the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1). Taken together, our data strongly suggests a role for TPP1 in endometrial receptivity via its effects on epithelial cell adhesion and suggests reduced levels associated with unexplained infertility may contribute to implantation failure.

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Matrix metalloproteinases improves trophoblast invasion and pregnancy potential in mice

Cited by 23 publications

References 35 publications

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Effect of hematopoietic progenitor cells on the biological characteristics of colon cancer tumor stem cells

Tripeptidyl peptidase I promotes human endometrial epithelial cell adhesive capacity implying a role in receptivity

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