Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: A possible role of the sirtuin 1 pathway

2013 ◽  
Vol 40 (3) ◽  
pp. 770-778 ◽  
Author(s):  
Ayumi Taguchi ◽  
Osamu Wada-Hiraike ◽  
Kei Kawana ◽  
Kaori Koga ◽  
Aki Yamashita ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Inflammatory Responses ◽  
Sirtuin 1 ◽  
Endometrial Stromal Cells

scholarly journals Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Haimiao Lv ◽  
Chenbo Yan ◽  
Lixin Deng ◽  
Zhan Peng ◽  
Dexin Yang ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Differentially Expressed ◽  
Flowering Plant ◽  
Interleukin 17 ◽  
Therapeutic Effects ◽  
Endometrial Stromal Cells ◽  
Forsythia Suspensa

Bovine endometrial stromal cells (bESCs) are exposed to a complex environment of bacteria and viruses due to the rupture of epithelial cells after delivery. Inflammatory responses are elicited by the activation of host pattern recognition receptors through pathogen-related molecules such as lipopolysaccharides (LPS) on the cell membrane. Forsythoside A (FTA) is a major active constituent of Forsythia suspensa (Thunb.) Vahl. is a flowering plant widely employed as a traditional Chinese herbal medicine to treat various inflammatory diseases such as nephritis, eye swelling, scabies, ulcers, and mastitis; however, the molecular mechanisms underlying its therapeutic effects on bovine endometritis are still unclear. The aim of this study was to explore the role of miRNA and the mechanisms underlying the protective activity of FTA on the inflammation of bovine endometrial stromal cells induced by LPS. Based on previous research, we isolated and cultured bESCs in vitro and categorized them into LPS and LPS+FTA groups with three replicates. Upon reaching 80% confluence, the bESCs were treated with 0.5 μg/mL of LPS or 0.5 μg/mL of LPS + 100 μg/mL of FTA. We, then, performed high-throughput sequencing (RNA-Seq) to investigate the effects of FTA on LPS-stimulated primary bESCs and their underlying mechanisms. We identified 167 miRNAs differentially expressed in the LPS groups; 72 miRNAs were up-regulated, and 95 were down-regulated. Gene ontology enrichment analysis revealed that differentially expressed microRNA (DEGs) were most enriched during the cellular metabolic process; they were mostly located intracellularly and participated in protein, enzyme, and ion binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were most enriched in the mitogen-activated protein kinase, tumor necrosis factor, and Interleukin-17 signaling pathways. These results reveal the complex molecular mechanism involved in the FTA and provide a basis for future studies of bovine endometritis treatment with traditional Chinese medicine monomer.

scholarly journals Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

2021 ◽  
Author(s):  
Dariusz Szukiewicz ◽  
Aleksandra Stangret ◽  
Carmen Ruiz-Ruiz ◽  
Enrique G. Olivares ◽  
Olga Soriţău ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Uterine Cavity ◽  
Retrograde Transport ◽  
Surrounding Tissue ◽  
Pelvic Cavity ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Estrogen Exposure ◽  
Chronic Inflammatory Condition

AbstractEndometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis.

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.

scholarly journals Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 295 ◽  
Author(s):  
Mohamed A. El-Mokhtar ◽  
Essam R. Othman ◽  
Maha Y. Khashbah ◽  
Ali Ismael ◽  
Mohamed AA Ghaliony ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Stromal Cells ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Endometrial Stromal Cells ◽  
Extrahepatic Replication ◽  
Efficient Replication ◽  
Over Time

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

scholarly journals Critical Role of TRPC1-Mediated Ca2+Entry in Decidualization of Human Endometrial Stromal Cells

2012 ◽  
Vol 26 (5) ◽  
pp. 846-858 ◽  
Author(s):  
Yasuhiro Kawarabayashi ◽  
Lin Hai ◽  
Akira Honda ◽  
Shinji Horiuchi ◽  
Hiroshi Tsujioka ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Critical Role ◽  
Endometrial Stromal Cells

scholarly journals The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage

2021 ◽  
Vol 3 ◽  
Author(s):  
Joanne Muter ◽  
Chow-Seng Kong ◽  
Jan J. Brosens
Keyword(s):  
Stromal Cells ◽  
Acute Stress ◽  
Embryo Implantation ◽  
Recurrence Risk ◽  
Tissue Remodelling ◽  
Endometrial Stromal Cells ◽  
Decidual Cells ◽  
Unk Cells ◽  
Acute Stress Response

In each menstrual cycle, the endometrium becomes receptive to embryo implantation while preparing for tissue breakdown and repair. Both pregnancy and menstruation are dependent on spontaneous decidualization of endometrial stromal cells, a progesterone-dependent process that follows rapid, oestrogen-dependent proliferation. During the implantation window, stromal cells mount an acute stress response, which leads to the emergence of functionally distinct decidual subsets, reflecting the level of replication stress incurred during the preceding proliferative phase. Progesterone-dependent, anti-inflammatory decidual cells (DeC) form a robust matrix that accommodates the conceptus whereas pro-inflammatory, progesterone-resistant stressed and senescent decidual cells (senDeC) control tissue remodelling and breakdown. To execute these functions, each decidual subset engages innate immune cells: DeC partner with uterine natural killer (uNK) cells to eliminate senDeC, while senDeC co-opt neutrophils and macrophages to assist with tissue breakdown and repair. Thus, successful transformation of cycling endometrium into the decidua of pregnancy not only requires continuous progesterone signalling but dominance of DeC over senDeC, aided by recruitment and differentiation of circulating NK cells and bone marrow-derived decidual progenitors. We discuss how the frequency of cycles resulting in imbalanced decidual subpopulations may determine the recurrence risk of miscarriage and highlight emerging therapeutic strategies.

scholarly journals Evolution of Conditional Cooperativity Between HOXA11 and FOXO1 Through Allosteric Regulation

2015 ◽  
Author(s):  
Mauris C. Nnamani ◽  
Soumya Ganguly ◽  
Vincent J. Lynch ◽  
Laura S. Mizoue ◽  
Yingchun Tong ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Allosteric Regulation ◽  
Multiple Roles ◽  
Physical Interaction ◽  
Functional Interaction ◽  
Endometrial Stromal Cells ◽  
Functional Roles ◽  
Functional Output

Transcription factors (TFs) play multiple roles in different cells and stages of development. Given this multitude of functional roles it has been assumed that TFs are evolutionarily highly constrained. Here we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs that play a key role in mammalian pregnancy, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires an interaction with FOXO1, and that the physical interaction between these proteins evolved long before their functional cooperativity. Through a combination of functional, biochemical, and structural approaches, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.

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