scholarly journals Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Dongfang Xiang ◽  
Min Zhao ◽  
Xiaofan Cai ◽  
Yongxia Wang ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
Epigenetic Modification ◽  
Uterine Cavity ◽  
Tissue Growth ◽  
Estrogen Receptor Β ◽  
Endometrial Cells

Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develop a potential therapeutic treatment based on the pathogenesis and mechanism of Endometriosis. Our preliminary data showed that the expression of estrogen receptor β (ERβ) was significantly increased, while ERα was significantly decreased, in endometriotic cells compared to normal endometrial cells. Further investigation showed that betulinic acid (BA) treatment suppressed ERβ expression through epigenetic modification on the ERβ promoter, while had no effect on ERα expression. In addition, BA treatment suppresses ERβ target genes, including superoxide dismutase 2 (SOD2), nuclear respiratory factor-1 (NRF1), cyclooxygenase 2 (COX2), and matrix metalloproteinase-1 (MMP1), subsequently increasing oxidative stress, triggering mitochondrial dysfunction, decreasing elevated proinflammatory cytokines, and eventually suppressing endometriotic cell proliferation, mimicking the effect of ERβ knockdown. On the other hand, gain of ERβ by lentivirus infection in normal endometrial cells resulted in increased cell proliferation and proinflammatory cytokine release, while BA treatment diminished this effect through ERβ suppression with subsequent oxidative stress and apoptosis. Our results indicate that ERβ may be a major driving force for the development of endometriosis, while BA inhibits Endometriosis through specific suppression of the ERβ signaling pathway. This study provides a novel therapeutic strategy for endometriosis treatment through BA-mediated ERβ suppression.

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

2020 ◽  
Vol 52 (10) ◽  
pp. 1102-1110
Author(s):  
Zhaodong Wang ◽  
Guangliang Zhang ◽  
Yingying Le ◽  
Jihui Ju ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
Skin Wound ◽  
Skin Tissue ◽  
Skin Wound Healing ◽  
Skin Tissue Engineering ◽  
Cyclin A2

Abstract Skin epidermal stem cells (EpSCs) play an important role in wound healing. Quercetin is a phytoestrogen reported to accelerate skin wound healing, but its effect on EpSCs is unknown. In this study, we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms. We found that quercetin at 0.1~1 μM significantly promoted EpSC proliferation and increased the number of cells in S phase. The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue. Mechanistic studies showed that quercetin significantly upregulated the expressions of β-catenin, c-Myc, and cyclins A2 and E1. Inhibitor for β-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation. The β-catenin inhibitor XAV-939 suppressed quercetin-induced expressions of β-catenin, c-Myc, and cyclins A2 and E1. The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin. Pretreatment of EpSCs with estrogen receptor (ER) antagonist ICI182780, but not the G protein-coupled ER1 antagonist G15, reversed quercetin-induced cell proliferation and upregulation of β-catenin, c-Myc, and cyclin A2. Collectively, these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation of β-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation. As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering, quercetin is a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering.

scholarly journals TEX11 Modulates Germ Cell Proliferation by Competing with Estrogen Receptor β for the Binding to HPIP

2012 ◽  
Vol 26 (4) ◽  
pp. 630-642 ◽  
Author(s):  
Yueh-Hsiang Yu ◽  
Fong-Ping Siao ◽  
Lea Chia-Ling Hsu ◽  
Pauline H. Yen
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Germ Cell ◽  
Estrogen Receptor Β ◽  
Germ Cell Proliferation

scholarly journals Silencing of Estrogen receptor β promotes the invasion and migration of osteosarcoma cells through activating Wnt signaling pathway

2019 ◽  
Author(s):  
Yiping Zhang ◽  
Changchang Yin ◽  
Xufeng Zhou ◽  
Yahua Wu ◽  
Lili Wang
Keyword(s):  
Estrogen Receptor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Estrogen Receptor Β ◽  
Migration And Invasion ◽  
Metastatic Tumors ◽  
Subcutaneous Tumor ◽  
Invasion And Migration ◽  
And Migration

Abstract Background This study aimed to evaluate the specific roles of Estrogen receptor β (ERβ) on the invasion and migration of osteosarcoma (OS) cells, and explore the regulatory mechanisms relating with Wnt signaling pathway. Methods The expression of ERβ was detected on human OS tissues by quantitative real-time PCR and immunohistochemistry. U2-OS cells were transfected with siRNA-ERβ (si-ERβ) to downrgulate ERβ, and treated with FH535 to inhibit Wnt signaling. The migration and invasion ability was detected by scratch and transwell assay, respectively. The expression of β-catenin, MMP-7 and MMP-9 was detected by Western blot. Subcutaneous tumor-bearing model was established by injection of U2-OS cells into mice, and the tumor volumes were measured. Orthotopic transplantation model was established by transplantation of tumor tissues into the liver of mice, and the metastatic tumors were counted. Results ERβ was downregulated in human OS tissues and U2-OS cells. The transfection of si-ERβ significantly increased the scratch healing rate, the number of invasion cells, and the expression of β-catenin, MMP-7 and MMP-9 in U2-OS cells. The injection of si-ERβ-transfected U2-OS cells into mice significantly increased the subcutaneous tumor volume, the expression of β-catenin, MMP-7 and MMP-9, and the number of metastatic tumors in liver tissues. The promoting effects of si-ERβ on the invasion and migration of U2-OS cells were significantly reversed by FH535 in vitro and vivo. Conclusions Silencing of ERβ promotes the invasion and migration of OS cells via activating Wnt signaling pathway.

scholarly journals Okadaic acid exposure induced neural tube defects in chicken (Gallus gallus) embryos

2020 ◽  
Author(s):  
Yu-hu Jiao ◽  
Guang Wang ◽  
Da-wei Li ◽  
Hong-ye Li ◽  
Jie-sheng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Okadaic Acid ◽  
Neural Tube ◽  
Gallus Gallus ◽  
Chick Embryos ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Receptor Signaling Pathway

Abstract Background Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and mainly responsible for diarrheic shellfish poisoning (DSP) in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. The embryotoxicity of OA is due to it can cross the placental barrier, which was proven in mice. However, there is no direct evidence of its developmental toxicity in human offspring. The chicken (Gallus gallus) embryo is a classic animal model for the studies of early vertebrate embryogenesis and late organogenesis due to its multiple advantages, such as convenience for observation, similarity to mammalian embryo, easy accessibility, and manipulation, etc. Results OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining demonstrated that OA exposure promoted cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increases in ROS content and SOD activity in the OA-exposed chicken embryos indicated that OA could result in the generation of oxidative stress in early chick embryos. The inhibition of BMP4 and Shh expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points. The expression of LBP, JUN, FOS, and CCL4 in Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with Toll-like receptor signaling pathway. Conclusion OA exposure can induce NTDs in chick embryos and increase the incidences of embryo mortality and malformation. Oxidative stress in early chick embryos may be subsequently responsible for the formation of NTDs. OA exposure can affect cell proliferation and apoptosis. Toll-like receptor signaling pathway may be responsible for the NTDs induced by OA.

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