scholarly journals Expression and the Biological Activities of Insulin-Like Growth Factor-Binding Protein Related Protein 1 in Rat Uterus during the Periimplantation Period

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5243-5251 ◽  
Author(s):  
Kazuhiro Tamura ◽  
Takahiko Hara ◽  
Masahiko Kutsukake ◽  
Ken Iwatsuki ◽  
Mayuko Yanagida ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Binding Protein ◽  
Biological Activities ◽  
Related Protein ◽  
Rat Uterus ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract IGF binding protein-related protein 1 (IGFBP-rP1) is highly expressed in the rat uterus around the time of implantation. In the present study, we determined the periimplantation localization of IGFBP-rP1 mRNA and assessed the effects of recombinant IGFBP-rP1 on the proliferative and prostacyclin (PGI2)-producing abilities of cultured endometrial cells early in pregnancy. IGFBP-rP1 mRNA was detected at high levels in endometrial stromal cells close to the smooth muscle of interimplantation sites around the time of implantation but absent from decidual zones surrounding the embryo. Differential uterine IGFBP-rP1 expression was also recognized in the delayed implanting pregnant model, but the level of mRNA decreased as decidual tissues formed in the decidualization model. Recombinant IGFBP-rP1 inhibited the proliferation of endometrial stromal cells in vitro and arrested them in the G1 phase of the cell cycle. Furthermore, IGFBP-rP1 significantly stimulated PGI2 synthesis and cyclooxygenase II mRNA expression in myometrial cells, both of which are essential molecules for successful implantation. These data suggest that IGFBP-rP1 is an implantation-associated protein and that it modulates the proliferation of rat uterine cells and their production of PGI2 during the periimplantation period.

scholarly journals Activation of SRC Kinase and Phosphorylation of Signal Transducer and Activator of Transcription-5 Are Required for Decidual Transformation of Human Endometrial Stromal Cells

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1227-1234 ◽  
Author(s):  
Takashi Nagashima ◽  
Tetsuo Maruyama ◽  
Hiroshi Uchida ◽  
Takashi Kajitani ◽  
Toru Arase ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Binding Protein ◽  
Phosphorylation Site ◽  
Src Kinase ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Signal Transducer ◽  
Endometrial Stromal Cells ◽  
Igf Binding ◽  
Igf Binding Protein

Progesterone induces decidual transformation of estrogen-primed human endometrial stromal cells (hESCs), critical for implantation and maintenance of pregnancy, through activation of many signaling pathways involving protein kinase A and signal transducer and activator of transcription (STAT)-5. We have previously shown that kinase activation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase is closely associated with decidualization and that SRC is indispensable for maximal decidualization in mice. To address whether SRC kinase activity is essential for decidualization in humans, hESCs were infected with adenoviruses carrying enhanced green fluorescent protein alone (Ad-EGFP), a kinase-inactive dominant-negative mutant (Ad-SRC/K295R), or an inactive autophosphorylation site mutant (Ad-SRC/Y416F). The cells were cultured in the presence of estradiol and progesterone (EP) to induce decidualization and subjected to RT-PCR, immunoblot, and ELISA analyses. Ad-EGFP-infected hESCs exhibited decidual transformation and up-regulation of decidualization markers including IGF binding protein 1 and prolactin in response to 12-d treatment with EP. In contrast, hESCs infected with Ad-SRC/K295R remained morphologically fibroblastoid without production of IGF binding protein 1 and prolactin even after EP treatment. Ad-SRC/Y416F displayed similar but less inhibitory effects on decidualization, compared with Ad-SRC/K295R. During decidualization, STAT5 was phosphorylated on tyrosine 694, a well-known SRC phosphorylation site. Phosphorylation was markedly attenuated by Ad-SRC/K295R but not Ad-EGFP. These results indicate that the SRC-STAT5 pathway is essential for decidualization of hESCs.

scholarly journals Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis

Reproduction ◽  
2018 ◽  
Author(s):  
Xuan-Tong Liu ◽  
Hui-Ting Sun ◽  
Zhong-Fang Zhang ◽  
Ru-Xia Shi ◽  
Li-Bing Liu ◽  
...  
Keyword(s):  
Nk Cells ◽  
Stromal Cells ◽  
Therapeutic Strategy ◽  
Neutralizing Antibody ◽  
Inhibitory Effect ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Indoleamine 2,3 Dioxygenase ◽  
Healthy Control

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO). Furthermore, IDO+NK cells possessed lower NKp46 and NKG2D but higher IL-10 than that of IDO-NK. Co-culture with endometrial stromal cells (nESCs) from healthy control or ectopic ESCs (eESCs) from women with EMS led to a significant increase in the IDO level in NK cells from peripheral blood, particularly eESCs, and an anti-TGF-β neutralizing antibody suppressed these effects in vitro. NK cells co-cultured with ESC more preferentially inhibited the viability of nESCs than eESCs did, and pretreating with 1-methyl-tryptophan (1-MT), an IDO inhibitor, reversed the inhibitory effect of NK cells on eESC viability. These data suggest that ESCs induce IDO+NK cells differentiation partly by TGF-β, and that IDO further restricts the cytotoxicity of NK cells in response to eESCs, which provides a potential therapeutic strategy for EMS patients, particularly those with a high number of impaired cytotoxic IDO+NK cells.

Major secretory protein of human decidualized endometrium in pregnancy is an insulin-like growth factor-binding protein

1988 ◽  
Vol 118 (2) ◽  
pp. 317-328 ◽  
Author(s):  
S. C. Bell ◽  
S. R. Patel ◽  
J. A. Jackson ◽  
G. T. Waites
Keyword(s):  
Growth Factor ◽  
Amniotic Fluid ◽  
Incubation Medium ◽  
Binding Protein ◽  
Secretory Protein ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

ABSTRACT Pregnancy-associated endometrial α1-globulin (α1-PEG) is quantitatively the major secretory protein product, synthesized and secreted in vitro, of the human decidualized endometrium during pregnancy. This protein has been purified from cytosolic extracts of this tissue and has now been characterized as a 32 kDa somatomedin/insulin-like growth factor (IGF)-binding protein. Immunoreactive α1-PEG isolated from amniotic fluid exhibited identical physiochemical properties and IGF-I-binding characteristics. In cytosolic extracts of pregnancy endometrium, in incubation medium of this tissue and in amniotic fluid, the 32 kDa protein represented the major α1-PEG immunoreactive protein and major IGF-I-binding component. Purified α1-PEG and incubation medium of pregnancy endometrium competed for IGF-I with placental membrane IGF receptors in vitro. The implications of the endometrial source of IGF-I-binding protein are dicussed with reference to the origin of the amniotic fluid and serum small Mr IGF-binding protein and to the suggested paracrine effect upon trophoblast proliferation. J. Endocr. (1988) 118, 317–328

Changes induced by non-enzymatic glycosylation of IGF-binding protein-3: effects on its binding properties and on its modulatory effect on IGF-I mitogenic action

1995 ◽  
Vol 144 (1) ◽  
pp. 119-126 ◽  
Author(s):  
A M Cortizo ◽  
J J Gagliardino
Keyword(s):  
Binding Protein ◽  
Mitogenic Activity ◽  
Dependent Manner ◽  
Binding Properties ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Enzymatic Glycosylation ◽  
Igfbp 3

Abstract The aim of this study was to demonstrate the feasibility of in vitro non-enzymatic glycosylation of IGF-binding protein-3 (IGFBP-3) and whether this process affects its binding properties and its modulatory effect on IGF-I mitogenic activity. Swiss 3T3 fibroblasts were cultured and the IGFBP-3 released into the medium (CM) glycated with either labelled or unlabelled glucose. Parallel glycation studies were performed using standard human IGFBP-3. Both species of IGFBP-3 became effectively glycated in a dose-dependent manner. Glycated IGFBP-3 bound larger amounts of 125I-labelled IGF-I than its non-glycated form. According to Scatchard analysis this effect might be due to an increase in the number of binding sites of the IGFBP-3 molecule rather than to changes in its affinity constants, which remain unchanged. Preincubation of fibroblasts with CM containing IGFBP-3 for 16 h before the addition of IGF-I enhanced the stimulatory effect of the hormone on thymidine incorporation into cell DNA. This potentiation was blunted when in vitro glycated instead of non-glycated IGFBP-3 was employed. These results provide further evidence of the in vitro glycation of IGFBP-3 and demonstrate that this process affects both its binding properties and its enhancing effect on IGF-I mitogenic activity. These changes may explain, at least partially, the development of many alterations observed in poorly controlled diabetic patients. Journal of Endocrinology (1995) 144, 119–126

scholarly journals Immunosuppressive Factor MNSFβ Regulates Cytokine Secretion by Mouse Lymphocytes and Is Involved in Interactions between the Mouse Embryo and Endometrial Cells In Vitro

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Yaping He ◽  
Zhaogui Sun ◽  
Yan Shi ◽  
Yahong Jiang ◽  
Zhefu Jia ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Cytokine Secretion ◽  
Embryonic Cells ◽  
Suppressor Factor ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Coculture Model ◽  
Mouse Lymphocytes

Immune tolerance at the fetomaternal interface must be established during the processes of implantation and pregnancy. Monoclonal nonspecific suppressor factor beta (MNSFβ) is a secreted protein that possesses antigen-nonspecific immune-suppressive function. It was previously reported that intrauterine immunoneutralization of MNSFβ significantly inhibited embryo implantation in mice. In the present study, MNSFβ protein expression was up- or downregulated by overexpression or RNA interference, respectively, in HCC-94 cells and the culture supernatants used to determine effects of MNSFβ on the secretion of IL-4 and TNFα from mouse lymphocytes as detected by ELISA. A coculture model of mouse embryos and endometrial stromal cells was also utilized to determine the effects of a specific anti-MNSFβ antibody on hatching and growth of embryos in vitro. The results show that MNSFβ induced secretion of IL-4 and inhibited secretion of TNFα from mouse lymphocytes. Following immunoneutralization of MNSFβ protein in the HCC-94 supernatant, the stimulatory effect of MNSFβ on IL-4 secretion from mouse lymphocytes was reduced, while the inhibitory effect on secretion of TNFα was abrogated. Expression of MNSFβ was detected in both embryonic and endometrial stromal cells, and its immunoneutralization inhibited the hatching and spreading of embryos in an in vitro coculture model. These results indicated that MNSFβ may play critical roles during the peri-implantation process by regulating cytokine secretion of lymphocytes and by mediating the crosstalk between embryonic cells and endometrial stromal cells.

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