scholarly journals ROS Are Critical for Endometrial Breakdown via NF-κB–COX-2 Signaling in a Female Mouse Menstrual-Like Model

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3638-3648 ◽  
Author(s):  
Bin Wu ◽  
Xihua Chen ◽  
Bin He ◽  
Shuyan Liu ◽  
Yunfeng Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cox 2 ◽  
Human Stromal Cells ◽  
Ros Scavengers

Abstract Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

scholarly journals Cyclooxygenase-2 Regulated by the Nuclear Factor-κB Pathway Plays an Important Role in Endometrial Breakdown in a Female Mouse Menstrual-like Model

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2900-2911 ◽  
Author(s):  
Xiangbo Xu ◽  
Xihua Chen ◽  
Yunfeng Li ◽  
Huizi Cao ◽  
Cuige Shi ◽  
...  
Keyword(s):  
Critical Role ◽  
Nuclear Factor Κb ◽  
Pcr Analysis ◽  
Pyrrolidine Dithiocarbamate ◽  
Nuclear Factor ◽  
Cox Inhibitor ◽  
Cox 2

Abstract The role of prostaglandins (PGs) in menstruation has long been proposed. Although evidence from studies on human and nonhuman primates supports the involvement of PGs in menstruation, whether PGs play an obligatory role in the process remains unclear. Although cyclooxygenase (COX) inhibitors have been used in the treatment of irregular uterine bleeding, the mechanism involved has not been elucidated. In this study, we used a recently established mouse menstrual-like model for investigating the role of COX in endometrial breakdown and its regulation. Administration of the nonspecific COX inhibitor indomethacin and the COX-2 selective inhibitor DuP-697 led to inhibition of the menstrual-like process. Furthermore, immunostaining analysis showed that the nuclear factor (NF)κB proteins P50, P65, and COX-2 colocalized in the outer decidual stroma at 12 to 16 hours after progesterone withdrawal. Chromatin immunoprecipitation analysis showed that NFκB binding to the Cox-2 promoter increased at 12 hours after progesterone withdrawal in vivo, and real-time PCR analysis showed that the NFκB inhibitors pyrrolidine dithiocarbamate and MG-132 inhibited Cox-2 mRNA expression in vivo and in vitro, respectively. Furthermore, COX-2 and NFκB inhibitors similarly reduced endometrial breakdown, suggesting that NFκB/COX-2-derived PGs play a critical role in this process. In addition, the CD45+ leukocyte numbers were sharply reduced following indomethacin (COX-1 and COX-2 inhibitor), DuP-697 (COX-2 inhibitor), and pyrrolidine dithiocarbamate (NFκB inhibitor) treatment. Collectively, these data indicate that NFκB/COX-2-induced PGs regulate leukocyte influx, leading to endometrial breakdown.

Role of nuclear factor-κB in gastric ulcer healing in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1296-G1304 ◽  
Author(s):  
Satoru Takahashi ◽  
Takuya Fujita ◽  
Akira Yamamoto
Keyword(s):  
Gastric Ulcer ◽  
Mrna Expression ◽  
Ulcer Healing ◽  
Nuclear Factor Κb ◽  
Normal Mucosa ◽  
Cyclooxygenase 2 ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Gastric Ulcer Healing

We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE2 production were also reduced. These results demonstrate that NF-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.

scholarly journals The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 479 ◽  
Author(s):  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Ariadna Pielok ◽  
Mateusz Sikora ◽  
Lukas Valihrach ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Nuclear Factor ◽  
Paracrine Signaling ◽  
Receptor Activator ◽  
The Impact

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

scholarly journals p62 acts as an oncogene and is targeted by miR-124-3p in glioma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Danni Deng ◽  
Kaiming Luo ◽  
Hongmei Liu ◽  
Xichen Nie ◽  
Lian Xue ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Nuclear Factor Κb ◽  
Autophagic Flux ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Human Glioma ◽  
Protein Levels ◽  
Novel Therapeutic

Abstract Background Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized. Methods We examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression. Results We revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3′-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression. Conclusions Our results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.

A novel role of l-serine (l-Ser) for the expression of nuclear factor of activated T cells (NFAT)2 in receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro

2006 ◽  
Vol 24 (5) ◽  
pp. 373-379 ◽  
Author(s):  
Takuya Ogawa ◽  
Norihiro Ishida-Kitagawa ◽  
Akira Tanaka ◽  
Takahiro Matsumoto ◽  
Tamayo Hirouchi ◽  
...  
Keyword(s):  
T Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Receptor Activator

EFFECTS OF FLUID SHEAR STRESS AND CIGLITAZONE ON OSTEOBLASTS

2012 ◽  
Vol 12 (04) ◽  
pp. 1250076
Author(s):  
LIJUN SUN ◽  
HAOYU WANG ◽  
HAO XU ◽  
JINHONG WEI ◽  
LIANG SHI ◽  
...  
Keyword(s):  
Shear Stress ◽  
Mrna Expression ◽  
Fluid Shear Stress ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Fluid Shear ◽  
Proliferation And Differentiation ◽  
Cox 2

Long-term use of thiazolidinedione (TZD) antidiabetic agents in patients with type 2 diabetes mellitus has been shown to increase the incidence of osteoporosis. Mechanical loading can enhance bone mass by promoting bone formation and suppressing bone resorption, which may be beneficial to patients with TZD-induced osteoporosis. In this study, we examined the cooperative effect of fluid shear stress (FSS) and ciglitazone (CIG), a type of TZD, on osteoblasts. The proliferation, osteoblast differentiation-related mRNA expression and translocation of nuclear factor κB (NFκB) of osteoblasts were assessed. The results show that CIG significantly decreased the proliferation of osteoblasts, inhibited the translocation of NFκB to the nucleus and reduced the mRNA expression of COX-2, IGF, Runx2 and OCN. At the same time, CIG also increased the mRNA expression of PPARγ. Conversely, FSS significantly increased the proliferation of osteoblasts, promoted the translocation of NFκB to the nucleus and increased the mRNA expression of COX-2, IGF, Runx2 and OCN but decreased the mRNA expression of PPARγ. When FSS and CIG were combined, FSS counteracted the effects of CIG on osteoblasts. Taken together, the current results suggest that FSS is able to arrest the effects of CIG on the proliferation and differentiation of osteoblasts.

scholarly journals A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-κB, COX-1, and COX-2

2007 ◽  
Vol 6 (8) ◽  
pp. 2319-2327 ◽  
Author(s):  
Ann S.J. Yeoh ◽  
Rachel J. Gibson ◽  
Eric E.K. Yeoh ◽  
Joanne M. Bowen ◽  
Andrea M. Stringer ◽  
...  
Keyword(s):  
Animal Model ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Fractionated Radiotherapy ◽  
Cox 2 ◽  
Cox 1

scholarly journals Role of Nuclear Factor-κB Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo

2002 ◽  
Vol 22 (5) ◽  
pp. 765-771 ◽  
Author(s):  
Alexander J. Chase ◽  
Mark Bond ◽  
Martin F. Crook ◽  
Andrew C. Newby
Keyword(s):  
Foam Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Macrophages

scholarly journals Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization

2019 ◽  
Vol 240 (3) ◽  
pp. 417-429 ◽  
Author(s):  
Vinay Shukla ◽  
Jyoti Bala Kaushal ◽  
Pushplata Sankhwar ◽  
Murli Manohar ◽  
Anila Dwivedi
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Nuclear Accumulation ◽  
Decidual Cell ◽  
Endometrial Stromal Cells ◽  
Cox 2 ◽  
Sirna Knockdown

Embryo implantation and decidualization are critical events that occur during early pregnancy. Decidualization is synchronized by the crosstalk of progesterone and the cAMP signaling pathway. Previously, we confirmed the role of TPPP3 during embryo implantation in mice, but the underlying role and mechanism of TPPP3 in decidualization has not yet been understood. The current study was aimed to investigate the role of TPPP3 in decidualization in vivo and in vitro. For in vivo experiments, decidual reaction was artificially induced in the uteri of BALB/c mice. TPPP3 was found to be highly expressed during decidualization, whereas in the uteri receiving TPPP3 siRNA, decidualization was suppressed and the expression of β-catenin and decidual marker prolactin was reduced. In human endometrium, TPPP3 protein was found to be predominantly expressed in the mid-secretory phase (LH+7). In the primary culture of human endometrial stromal cells (hESCs), TPPP3 siRNA knockdown inhibited stromal-to-decidual cell transition and decreased the expression of the decidualization markers prolactin and IGFBP-1. Immunofluorescence and immunoblotting experiments revealed that TPPP3 siRNA knockdown suppressed the expression of β-catenin, NF-κB and COX-2 in hESCs during decidualization. TPPP3 inhibition also decreased NF-kB nuclear accumulation in hESCs and suppressed NF-κB transcriptional promoter activity. COX-2 expression was significantly decreased in the presence of a selective NF-kB inhibitor (QNZ) implicating that NF-kB is involved in COX-2 expression in hESCs undergoing decidualization. TUNEL assay and FACS analysis revealed that TPPP3 knockdown induced apoptosis and caused loss of mitochondrial membrane potential in hESCs. The study suggested that TPPP3 plays a significant role in decidualization and its inhibition leads to the suppression of β-catenin/NF-κB/COX-2 signaling along with the induction of mitochondria-dependent apoptosis.

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