scholarly journals Prostaglandin F2α promotes angiogenesis and embryo–maternal interactions during implantation

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 539-552 ◽  
Author(s):  
Piotr Kaczynski ◽  
Mariusz P Kowalewski ◽  
Agnieszka Waclawik
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Prostaglandin F2α ◽  
Expression Of Genes ◽  
Interleukin 1Α ◽  
Extraembryonic Membranes ◽  
Endothelial Growth Factor

AbstractImplantation in humans and other mammals is a critical period during which high embryonic mortality rates occur. Prostaglandins (PGs) are key mediators regulating interactions between the reproductive tract and the conceptus (embryo with extraembryonic membranes). Although the significance of PGF2α as a regulator of corpus luteum regression is well established, the role of its high amounts in the uterine lumen in most mammals, regardless of placentation type, during the implantation period remains unresolved. We hypothesized that PGF2α acting as an embryonic signal mediator contributes to pregnancy establishment. Using a porcine model, we demonstrated that the conceptus and its signal (estradiol-17β) elevated endometrial expression of PGF2α receptor (PTGFR)invivoandin vitro. PTGFR protein was expressed mainly in luminal epithelial (LE) and glandular epithelial cells and blood vessels in the endometrium. PGF2α stimulated the MAPK1/3 pathway in endometrial LE cells that coincided with elevated gene expression and secretion of endometrial vascular endothelial growth factor A (VEGFA) protein. PGF2α–PTGFR and adenylyl cyclase signaling were involved in this process. PGF2α-induced VEGFA acting through its receptors stimulated proliferation of endometrial endothelial cells. Moreover, PGF2α elevated gene expression of biglycan, matrix metalloproteinase 9, transforming growth factor β3, and interleukin 1α in the endometrium. In summary, our study indicates that PGF2α participates in pregnancy establishment by promoting angiogenesis and expression of genes involved in tissue remodeling and conceptus–maternal interactions in porcine endometrium during early pregnancy.

scholarly journals Semen Modulates Inflammation and Angiogenesis in the Reproductive Tract of Female Rabbits

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2207
Author(s):  
Jaume Gardela ◽  
Amaia Jauregi-Miguel ◽  
Cristina A. Martinez ◽  
Heriberto Rodríguez-Martinez ◽  
Manel López-Béjar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Breeding Systems ◽  
Preimplantation Embryos ◽  
Natural Mating ◽  
Anti Inflammatory

The maternal environment modulates immune responses to facilitate embryo development and ensure pregnancy. Unraveling this modulation could improve the livestock breeding systems. Here it is hypothesized that the exposure of the female rabbit reproductive tract to semen, as well as to early embryos, modulates inflammation and angiogenesis among different tissue segments. qPCR analysis of the gene expression changes of the anti-inflammatory interleukin-10 (IL10) and transforming growth factor beta family (TGFβ1–3) and the angiogenesis mediator vascular endothelial growth factor (VEGF-A) were examined in response to mating or insemination with sperm-free seminal plasma (SP). Reproductive tract segment (cervix to infundibulum) samples were obtained in Experiment 1, 20 h after gonadotropin-releasing hormone (GnRH) stimulation (control), natural mating (NM) or vaginal infusion with sperm-free SP (SP-AI). Additionally, segmented samples were also obtained at 10, 24, 36, 68 or 72 h after GnRH-stimulation and natural mating (Experiment 2). The results of gene expression, analyzed by quantitative PCR, showed that NM effects were mainly localized in the uterine tissues, depicting clear temporal variation, while SP-AI effects were restricted to the oviduct. Changes in anti-inflammatory and angiogenesis mediators indicate an early response in the uterus and a late modulation in the oviduct either induced by semen or preimplantation embryos. This knowledge could be used in the implementation of physiological strategies in breeding systems to face the new challenges on rabbit productivity and sustainability.

Vascular Endothelial Growth Factor Expression in Peritoneal Mesothelial Cells Undergoing Transdifferentiation

2008 ◽  
Vol 28 (5) ◽  
pp. 497-504 ◽  
Author(s):  
Jing Zhang ◽  
Kook-Hwan Oh ◽  
Hui Xu ◽  
Peter J. Margetts
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Vascular Endothelial ◽  
Alpha Smooth Muscle Actin ◽  
Peritoneal Tissue ◽  
Peritoneal Mesothelium ◽  
Endothelial Growth Factor

Objective To analyze gene expression of localized peritoneal tissue structures in a rodent model of peritoneal fibrosis. Methods Female Sprague Dawley rats were treated with an intraperitoneal injection of an adenovirus expressing active transforming growth factor-beta or control adenovirus. Four and 7 days after infection, animals were sacrificed and frozen sections of parietal peritoneum were subjected to immunofluorescence-aided laser capture microdissection in order to isolate vascular, mesothelial, and submesothelial structures. RNA was extracted from microdissected tissue and gene expression was analyzed by quantitative reverse-transcript polymerase chain reaction. We analyzed genes involved in angiogenesis, epithelial-to-mesenchymal transdifferentiation, and fibrosis. Vascular endothelial growth factor and alpha-smooth muscle actin expression was analyzed with immunohistochemistry of formalin-fixed tissue. Results Transforming growth factor-β1 induced expression of Snail and alpha-smooth muscle actin genes in the peritoneal mesothelium. This same cell population also demonstrated increased gene expression of vascular endothelial growth factor. The distribution of this growth factor was confirmed by immunohistochemistry. The fibrogenic growth factor, connective tissue growth factor, was also strongly induced in the peritoneal mesothelium. Conclusions Using immunofluorescence-aided laser capture microdissection, we were able to study gene expression in subcompartments of the peritoneal tissue. We demonstrated that mesothelial cells exhibiting mesenchymal transdifferentiation are associated with increased expression of genes associated with fibrosis and angiogenesis.

Profibrogenic phenotype in caveolin-1 deficiency via differential regulation of STAT-1/3 proteins

2014 ◽  
Vol 92 (5) ◽  
pp. 370-378 ◽  
Author(s):  
Stefan W. Ryter ◽  
Augustine M.K. Choi ◽  
Hong Pyo Kim
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Tyrosine Phosphatase ◽  
Transforming Growth Factor Β ◽  
Lung Fibroblasts ◽  
Caveolin 1 ◽  
Expression Of Genes ◽  
Liver And Kidney

Fibrosis underlies the pathogenesis of several human diseases, which can lead to severe injury of vital organs. We previously demonstrated that caveolin-1 expression is reduced in experimental fibrosis and that caveolin-1 exerts antiproliferative and antifibrotic effects in lung fibrosis models. The signal transducers and activators of transcription (STAT) proteins, STAT1 and STAT3, can be activated simultaneously. STAT1 can inhibit cell growth and promote apoptosis while STAT3 inhibits apoptosis. Here, we show that caveolin-1-deficient (cav-1−/−) lung fibroblasts display dramatically upregulated STAT3 activation in response to platelet-derived growth factor-BB and transforming growth factor-β stimuli, whereas STAT1 activation is undetectable. Downregulation of protein tyrosine phosphatase-1B played a role in the preferential activation of STAT3 in cav-1−/− fibroblasts. Genetic deletion of STAT3 by siRNA modulated the expression of genes involved in cell proliferation and fibrogenesis. Basal expression of α-smooth muscle actin was prominent in cav-1−/− liver and kidney, consistent with deposition of collagen in these organs. Collectively, we demonstrate that the antiproliferative and antifibrogenic properties of caveolin-1 in vitro are mediated by the balance between STAT1 and STAT3 activation. Deregulated STAT signaling associated with caveolin-1 deficiency may be relevant to proliferative disorders such as tissue fibrosis.

scholarly journals Limited role for transforming growth factor–β pathway activation-mediated escape from VEGF inhibition in murine glioma models

2016 ◽  
Vol 18 (12) ◽  
pp. 1610-1621 ◽  
Author(s):  
Davide Mangani ◽  
Michael Weller ◽  
Emad Seyed Sadr ◽  
Edith Willscher ◽  
Katharina Seystahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Single Agent ◽  
Immune Response Gene ◽  
Tumor Control ◽  
Vegf Inhibition ◽  
Murine Glioma

AbstractBackgroundThe vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)–β pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition.MethodsThe role of the TGF-β pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models.ResultsWe found that TGF-β is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-β pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-β receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of tumor volume and blood vessel density, but not induction of hypoxia, correlated with benefit from B20-4.1.1. Reduction of phosphorylated (p)SMAD2 by LY2157299 was seen in all models but did not predict survival. Resistance to B20 was associated with anti-angiogenesis escape pathway gene expression, whereas resistance to LY2157299 was associated with different immune response gene signatures in SMA-497 and GL-261 on transcriptomic profiling. The combination of B20 with LY2157299 was ineffective in SMA-497 but provided prolongation of survival in GL-261, associated with early suppression of pSMAD2 in tumor and host immune cells, prolonged suppression of angiogenesis, and delayed accumulation of tumor infiltrating microglia/macrophages.ConclusionsOur study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-β pathways might lead to improved tumor control only in subsets of glioblastoma.

Prostaglandin F2α–PTGFR signalling activation, growth factor expression and cell proliferation in bovine endometrial explants

2017 ◽  
Vol 29 (11) ◽  
pp. 2195 ◽  
Author(s):  
Shuangyi Zhang ◽  
Bo Liu ◽  
Long Gao ◽  
Wei Mao ◽  
Changqi Fu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Expression ◽  
Transforming Growth Factor ◽  
Prostaglandin F2α ◽  
Transforming Growth Factor Β1 ◽  
Specific Protein ◽  
Tissue Growth ◽  
Nuclear Antigen

The endometrium of domestic animals undergoes regular periods of regeneration and degeneration and exhibits a remarkable capacity for self-repair during the oestrous cycle. The endometrial growth pattern is also observed during in the implantation period and early pregnancy, but the mechanism underlying endometrial growth in these processes remains unclear. A positive correlation between endometrial growth in these processes and prostaglandin (PG) F2α secretion has been reported, but the roles that PGF2α plays in endometrial growth is less studied. In the present study, cell proliferation and the responses of a series of growth factors essential for endometrial growth to PGF2α receptor (PTGFR) activation were investigated in bovine endometrial explants in vitro. Using real-time reverse transcription–polymerase chain reaction and western blotting, mRNA and protein expression of connective tissue growth factor, fibroblast growth factor2, interleukin8, matrix metalloproteinase2, transforming growth factor β1 and vascular endothelial growth factor A was increased (P < 0.05) and cell proliferation, including epithelial and fibroblast proliferation, was induced in response to increased levels of proliferating cell nuclear antigen, cytokeratin-18 and fibroblast-specific protein-1 (P < 0.05) following PTGFR activation by adding fluprostenol (10−9–10−5 M) into culture medium of bovine endometrial explants. However, caspase-3 protein expression was reduced following treatment of explants with fluprostenol (10−9–10−5 M, P < 0.05). These results may help define the possible roles the PGF2α–PTGFR signalling pathway plays in endometrial growth.

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