scholarly journals Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1233-1239 ◽  
Author(s):  
Tomonori Ishikawa ◽  
Tatsuya Harada ◽  
Toshiro Kubota ◽  
Takeshi Aso
Keyword(s):  
Matrix Metalloproteinase ◽  
Stromal Cells ◽  
Human Endometrium ◽  
Dependent Manner ◽  
Endometrial Stromal Cells ◽  
Functional Changes ◽  
Matrix Metalloproteinase 1 ◽  
Human Uterine Endometrium

Androgen receptor (AR) is reported to be expressed in human uterine endometrium, but not much information is available on the role of androgens in human endometrium. The purpose of this study is to investigate the role of androgens in the regulation of matrix metalloproteinase (MMP)-1, which is one of the important MMPs for menstruation and embryo implantation in human endometrium. Human endometrial stromal cells (HESCs) were obtained from human endometrium by enzymatic dissociation method. Purified HESCs were incubated with 17β-estradiol (E2), testosterone, or E2 + testosterone. Progestins (natural progesterone or medroxyprogesterone acetate) or vehicle (dimethyl sulfoxide) were also added to the media instead of testosterone. Furthermore, hydroxyflutamide (FLU),a specific AR antagonist, was also supplemented to cultured media. The amounts of MMP-1 in cultured media and in HESC lysates were examined by ELISA measurements and western blotting analysis respectively. The expression of ARmRNA in HESCs RNA was analyzed by RT-PCR. Testosterone significantly inhibited MMP-1 in both cultured media and cell lysates in a dose-dependent manner. Progestins also inhibited MMP-1. Furthermore, FLU completely recovered the decrease of MMP-1 induced by testosterone. ARmRNA was detected in all HESCs RNA. The present study demonstrated that the secretion and production of MMP-1 in HESCsin vitrowere inhibited by testosterone through androgen receptors in a manner similar to that seen for progesterone. These findings indicate that androgen may play an important role in morphological and functional changes of human endometrium.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

Effects of Celecoxib and Nimesulide on the Proliferation of Ectopic Endometrial Stromal Cells in vitro

2008 ◽  
Vol 36 (5) ◽  
pp. 1032-1038 ◽  
Author(s):  
B Kong ◽  
Y Tian ◽  
W Zhu ◽  
S Su ◽  
Y Kan
Keyword(s):  
Cell Cycle ◽  
Stromal Cells ◽  
Prostaglandin E ◽  
Apoptotic Cells ◽  
Dependent Manner ◽  
Selective Inhibitors ◽  
Endometrial Stromal Cells ◽  
Cox 2 ◽  
Dose Dependent

The effects of cyclooxygenase 2 (COX-2) selective inhibitors on the proliferation of ectopic endometrial stromal cells in vitro were investigated. Ectopic endometrial stromal cells were treated with either celecoxib or nimesulide for 24 and 48 h. The results showed that (i) both celecoxib and nimesulide inhibited the proliferation of ectopic endometrial stromal cells in vitro in a time- and dose-dependent manner; (ii) the expression of prostaglandin E2 was significantly inhibited by both celecoxib and nimesulide in a dose-dependent manner; (iii) the percentage of apoptotic cells was significantly higher for cells treated with celecoxib or nimesulide than for untreated cells; and (iv) the percentage of the cells in the G0/G1 phase increased after the cells were treated with either agent in a dose-dependent manner. These data suggest that celecoxib and nimesulide inhibited proliferation of ectopic endometrial stromal cells by inducing apoptosis and blocking the cell cycle at the G0/G1 phase.

Cyclic Changes in the Expression ofp57kip2in Human Endometrium and its Regulation by Steroid Hormones in Endometrial Stromal Cells In Vitro

2011 ◽  
Vol 19 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Sung Tae Kim ◽  
Sung Ki Lee ◽  
Myung Chan Gye
Keyword(s):  
Steroid Hormones ◽  
Stromal Cells ◽  
Human Endometrium ◽  
Endometrial Stromal Cells ◽  
Cyclic Changes

The role of stromal cells in the expression of interstitial collagenase (matrix metalloproteinase-1) in the invasion of gastric cancer

1997 ◽  
Vol 66 (3) ◽  
pp. 168-172 ◽  
Author(s):  
Yoshihiko Sakurai ◽  
Yoshihide Otani ◽  
Kaori Kameyama ◽  
Naoki Igarashi ◽  
Tetsuro Kubota ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Matrix Metalloproteinase ◽  
Stromal Cells ◽  
Matrix Metalloproteinase 1 ◽  
Interstitial Collagenase

scholarly journals Progesterone Enhances Interleukin-15 Production in Human Endometrial Stromal Cells in Vitro1

2000 ◽  
Vol 85 (12) ◽  
pp. 4765-4770 ◽  
Author(s):  
Hidetaka Okada ◽  
Tatsuya Nakajima ◽  
Mayumi Sanezumi ◽  
Akiko Ikuta ◽  
Katsuhiko Yasuda ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Stromal Cells ◽  
Hormonal Control ◽  
Human Endometrium ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Endometrial Stromal Cells ◽  
Potent Inducer ◽  
Interleukin 15

Interleukin-15 (IL-15) is a novel cytokine that stimulates lymphocyte proliferation and migration via a trimeric receptor sharing the β andγ signal-transducing chains with the IL-2 receptor. It is suggested that IL-15 is involved in regulating the proliferation and differentiation of uterine natural killer cells. In the human endometrium, we have recently reported that IL-15 messenger ribonucleic acid (mRNA) levels significantly increased during the secretory phase compared with those during the proliferative phase. In this study we investigated whether the female sex steroids progesterone (P) and estradiol (E2) regulate IL-15 messenger RNA (mRNA) and the secretion in human endometrial stromal cells (ESC) in vitro. Northern blot analyses revealed a significant increase in IL-15 mRNA levels in ESC treated with P alone or E2 plus P compared with vehicle. Furthermore, P is a potent inducer of IL-15 mRNA expression in ESC in a dose-dependent manner. On the other hand, E2 alone did not increase IL-15 mRNA expression. By enzyme-linked immunosorbent assay, IL-15 protein secretion was stimulated by P and further enhanced by combined treatment with E2 and P, whereas E2 alone was ineffective. It is suggested that IL-15 is deeply involved in the hormonal control of the human endometrium by P and E2.

scholarly journals Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Naoko Kida ◽  
Yoshiyuki Matsuo ◽  
Yoshiko Hashimoto ◽  
Kenichiro Nishi ◽  
Tomoko Tsuzuki-Nakao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Protein Stabilization ◽  
Human Endometrium ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Endometrial Stromal Cells ◽  
Hypoxic Conditions

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.

scholarly journals Macrophages promote the growth and invasion of endometrial stromal cells by downregulating IL-24 in endometriosis

Reproduction ◽  
2016 ◽  
Vol 152 (6) ◽  
pp. 673-682 ◽  
Author(s):  
Jun Shao ◽  
Bing Zhang ◽  
Jia-Jun Yu ◽  
Chun-Yan Wei ◽  
Wen-Jie Zhou ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Neutralizing Antibody ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
Nuclear Antigen ◽  
Metastasis Suppressor ◽  
Dependent Manner ◽  
Ki 67 ◽  
Endometrial Stromal Cells

Macrophages play an important role in the origin and development of endometriosis. Estrogen promoted the growth of decidual stromal cells (DSCs) by downregulating the level of interleukin (IL)-24. The aim of this study was to clarify the role and mechanism of IL-24 and its receptors in the regulation of biological functions of endometrial stromal cells (ESCs) during endometriosis. The level of IL-24 and its receptors in endometrium was measured by immunohistochemistry.In vitroanalysis was used to measure the level of IL-24 and receptors and the biological behaviors of ESCs. Here, we found that the expression of IL-24 and its receptors (IL-20R1 and IL-20R2) in control endometrium was significantly higher than that in eutopic and ectopic endometrium of women with endometriosis. Recombinant human IL-24 (rhIL-24) significantly inhibited the viability of ESCs in a dosage-dependent manner. Conversely, blocking IL-24 with anti-IL-24 neutralizing antibody promoted ESCs viability. In addition, rhIL-24 could downregulate the invasiveness of ESCsin vitro. After co-culture, macrophages markedly reduced the expression of IL-24 and IL-20R1 in ESCs, but not IL-22R1. Moreover, macrophages significantly restricted the inhibitory effect of IL-24 on the viability, invasion, the proliferation relative gene Ki-67, proliferating cell nuclear antigen (PCNA) and cyclooxygenase2 (COX-2), and the stimulatory effect on the tumor metastasis suppressor gene CD82 in ESCs. These results indicate that the abnormally low level of IL-24 in ESCs possibly induced by macrophages may lead to the enhancement of ESCs’ proliferation and invasiveness and contribute to the development of endometriosis.

scholarly journals Downregulation of decidual SP1 and P300 is associated with severe preeclampsia

2018 ◽  
Vol 60 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Yachao Zhang ◽  
Jieqiong Yang ◽  
Shijian Lv ◽  
Dong-Qin Zhao ◽  
Zi-Jiang Chen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Rna Interference ◽  
Growth Factor ◽  
Tissue Factor ◽  
Stromal Cells ◽  
Vascular Endothelial ◽  
Endometrial Stromal Cells ◽  
Endothelial Growth Factor

Preeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria after 20 weeks of gestation, affecting 5–7% of pregnancies worldwide. So far, the etiology of PE remains poorly understood. Abnormal decidualization is thought to contribute to the development of PE. SP1 belongs to the Sp/KLF superfamily and can recruit P300 to regulate the transcription of several genes. SP1 is also very important for decidualization as it enhances the expression of tissue factor. In this study, we investigated the expression of SP1 and P300 in deciduae and their relationship with PE. A total of 42 decidua samples were collected, of which 21 were from normal pregnant (NP) and 21 from severe PE. SP1 and P300 expression in deciduae and the levels of SP1 and P300 in cultured human endometrial stromal cells (hESCs) and primary hESCs during decidualization were determined. To further investigate the role of SP1 and P300 in human decidualization, RNA interference was used to silence SP1 and P300 in hESCs and primary hESCs. The following results were obtained. We found that the expressions of SP1 and P300 were reduced in decidual tissues with PE compared to those from NP. In thein vitromodel of induction of decidualization, we found an increase in bothSP1andP300levels. Silencing ofSP1andP300resulted in abnormal decidualization and a significant reduction of decidualization markers such as insulin-like growth factor-binding protein1 and prolactin. Furthermore, the expression of vascular endothelial growth factor was also decreased uponSP1andP300silencing. Similar results were observed in primary hESCs. Our results suggest that SP1 and P300 play an important role during decidualization. Dysfunction of SP1 and P300 leads to impaired decidualization and might contribute to PE.

scholarly journals Role of Versican in the Pathogenesis of Peritoneal Endometriosis

2016 ◽  
Vol 101 (11) ◽  
pp. 4349-4356 ◽  
Author(s):  
Hirohiko Tani ◽  
Yukiyasu Sato ◽  
Masashi Ueda ◽  
Yumiko Miyazaki ◽  
Koh Suginami ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Chinese Hamster Ovary Cells ◽  
Cell Monolayer ◽  
Chinese Hamster ◽  
Endometrial Stromal Cells ◽  
Matrigel Invasion ◽  
Molecular Alterations ◽  
Peritoneal Endometriosis

Context: Sampson’s theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum). Versican, a major proteoglycan component of the extracellular matrix, is one of the molecules up-regulated in endometriotic peritoneum. Objective: To investigate the role of versican in peritoneal endometriosis. Design, Patients, and Main Outcome Measure: Endometriotic peritoneum and non-endometriotic peritoneum were subjected to RT-PCR, immunostaining, and Western blotting. The versican V1 isoform was stably transfected into Chinese hamster ovary cells (CHO-V1), and the effects of CHO-V1-derived conditioned medium (V1-CM) on primary human endometrial stromal cells were investigated with attachment, invasion, and proliferation assays. The effects of peritoneal fluid collected from endometriotic women (endometriotic PF) or cytokines/growth factors, which were shown to be elevated in endometriotic PF, on versican expression in a human peritoneal cell line (HMrSV5) were also examined. Results: Versican V1 expression levels were significantly higher in endometriotic peritoneum. In vitro, V1-CM promoted attachment to the HMrSV5 cell monolayer as well as the Matrigel invasion of endometrial stromal cells. Although versican V1 expression was up-regulated by TGF-β1 in HMrSV5 cells, it remained unchanged in endometriotic PF. Conclusions: Our results suggest the involvement of peritoneal versican in the development of peritoneal endometriosis.

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