scholarly journals Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice

2019 ◽  
Vol 23 (4) ◽  
pp. 251 ◽  
Author(s):  
Qi Huang ◽  
Lele Han ◽  
Rong Lv ◽  
Ling Ling
Keyword(s):  
Signal Transduction ◽  
Notch Signaling ◽  
Signaling Pathways ◽  
Janus Kinase ◽  
Activation Of Transcription ◽  
Th17 Cytokines

Ο ρόλος των STAT μεταγραφικών παραγόντων στην οξεία λεμφοβλαστική λευχαιμία της παιδικής ηλικίας

2019 ◽  
Author(s):  
Μαρία Τσότρα
Keyword(s):  
Signaling Pathways ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Activation Of Transcription

Οι νεοπλασίες της παιδικής ηλικίας αφορούν μόνο το 2% του συνόλου των κακοηθών νοσημάτων στις αναπτυγμένες χώρες. Τις τελευταίες δεκαετίες έχει σημειωθεί σημαντική πρόοδος, τόσο στη διάγνωση, όσο και στην αντιμετώπιση των νοσημάτων αυτών. Αυτό έχει ως αποτέλεσμα, ένα νόσημα που παλαιότερα θεωρείτο «θανατηφόρο», σήμερα, με την βελτίωση των διαγνωστικών και θεραπευτικών μεθόδων, να θεωρείται «ιάσιμο». Επιδημιολογικές μελέτες έχουν προσπαθήσει κατά καιρούς να αναδείξουν τους πιθανούς παράγοντες που συμβάλλουν στην εμφάνιση των κακοηθών νοσημάτων της παιδικής ηλικίας. Οι λευχαιμίες, και κυρίως η ΟΛΛ, έχουν μελετηθεί περισσότερο. Στους πιθανούς παράγοντες κινδύνου περιλαμβάνονται γενετικοί παράγοντες, περιβαλλοντικοί παράγοντες, καθώς και ιογενείς λοιμώξεις. Στην προσπάθεια ανάδειξης των πιθανών μηχανισμών που εμπλέκονται στη λευχαιμογένεση, το ενδιαφέρον των πιο πρόσφατων ερευνών έχει στραφεί στους γενετικούς παράγοντες, στοχεύοντας κυρίως στην καλύτερη κατανόηση αλλά και στην αντιμετώπιση του νοσήματος με πιο ειδικά θεραπευτικά μέσα. Αν και η επίδραση των παραπάνω παραγόντων στην εμφάνιση της λευχαιμίας είναι σαφώς καθορισμένη, οι ενδοκυττάριοι μηχανισμοί που μεσολαβούν δεν έχουν διευκρινιστεί πλήρως. Σημαντικό ρόλο φαίνεται να κατέχουν τα ενδοκυττάρια μονοπάτια αγωγής σήματος ( Signaling pathways). Μια από τις κυριότερες ενδοκυττάριες σηματοδοτήσεις αποτελεί η οδός Janus Kinase / Signal Transducer and Activation of Transcription (JAK/STAT). Η σχέση των STAT με βασικά γονίδια υποδεικνύουν τον σημαντικό ρόλο της ενδοκυττάριας αυτής οδού στην αιμοποίηση και στην ρύθμιση της λειτουργίας των αιμοποιητικών κυττάρων. Επιπλέον μεταβολές της JAK/STAT οδού έχουν συσχετιστεί άμεσα ή έμμεσα με αιματολογικά νοσήματα.Αντικατοπτρίζοντας τον σημαντικό τους ρόλο στην κυτταρική ανάπτυξη και διαφοροποίηση, αρκετές μελέτες έχουν αναδείξει την παθολογική ενεργοποίηση των STAT σε συμπαγείς όγκους και σε αιματολογικές κακοήθειες. Ειδικότερα όμως, η συνεχής ενεργοποίηση των STAT1 και κυρίως STAT3, STAT5a και STAT5b, έχει καταγραφεί τόσο στις οξείες όσο και στις χρόνιες λευχαιμίες, συσχετίζοντας τους και με συγκεκριμένες χρωμοσωμικές ανωμαλίες που σχετίζονται με την πρόγνωση της νόσου. Συγκεκριμένα οι FLT3-ITD θετικές λευχαιμίες (ΟΛΛ και ΟΜΛ), που χαρακτηρίζονται από δυσμενή πρόγνωση, ενεργοποιούν το STAT μεταγραφικό μονοπάτι. Συνεπώς, ένα ενδοκυττάριο μονοπάτι μεταγωγής σήματος που θα μπορούσε, αναμφισβήτητα, να αποτελέσει αντικείμενο μελέτης στα πλαίσια ανάπτυξης στοχευμένης θεραπείας, είναι αυτό των STAT μεταγραφικών παραγόντων. Η παρούσα μελέτη στοχεύει στην ταυτοποίηση της ενεργοποίησης των STAT γονιδίων στην παιδική ΟΛΛ καθώς και την ανάδειξη οποιαδήποτε πιθανής συσχέτισης της με συγκεκριμένα κυτταρογενετικά χαρακτηριστικά ή στάδια ωρίμανσης του λευχαιμικού κυττάρου, δηλαδή του ανοσοφαινότυπου της λευχαιμίας. Επιπλέον μελετήσαμε και την έκφραση των STAT γονιδίων σε σχέση με την ελάχιστη υπολειπόμενη νόσο και την επιβίωση.

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

scholarly journals Inflammation and tumor progression: signaling pathways and targeted intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Lei Wu ◽  
Guifang Yan ◽  
Yu Chen ◽  
Mingyue Zhou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Response To Therapy ◽  
Janus Kinase ◽  
Oncolytic Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Resolution Of Inflammation ◽  
Chemokine Ligands

AbstractCancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

scholarly journals cROStalk for Life: Uncovering ROS Signaling in Plants and Animal Systems, from Gametogenesis to Early Embryonic Development

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 525
Author(s):  
Valentina Lodde ◽  
Piero Morandini ◽  
Alex Costa ◽  
Irene Murgia ◽  
Ignacio Ezquer
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Analytical Techniques ◽  
Antioxidant Systems ◽  
Developmental Studies ◽  
Science Field ◽  
Ros Signaling ◽  
Reproductive Processes

This review explores the role of reactive oxygen species (ROS)/Ca2+ in communication within reproductive structures in plants and animals. Many concepts have been described during the last years regarding how biosynthesis, generation products, antioxidant systems, and signal transduction involve ROS signaling, as well as its possible link with developmental processes and response to biotic and abiotic stresses. In this review, we first addressed classic key concepts in ROS and Ca2+ signaling in plants, both at the subcellular, cellular, and organ level. In the plant science field, during the last decades, new techniques have facilitated the in vivo monitoring of ROS signaling cascades. We will describe these powerful techniques in plants and compare them to those existing in animals. Development of new analytical techniques will facilitate the understanding of ROS signaling and their signal transduction pathways in plants and mammals. Many among those signaling pathways already have been studied in animals; therefore, a specific effort should be made to integrate this knowledge into plant biology. We here discuss examples of how changes in the ROS and Ca2+ signaling pathways can affect differentiation processes in plants, focusing specifically on reproductive processes where the ROS and Ca2+ signaling pathways influence the gametophyte functioning, sexual reproduction, and embryo formation in plants and animals. The study field regarding the role of ROS and Ca2+ in signal transduction is evolving continuously, which is why we reviewed the recent literature and propose here the potential targets affecting ROS in reproductive processes. We discuss the opportunities to integrate comparative developmental studies and experimental approaches into studies on the role of ROS/ Ca2+ in both plant and animal developmental biology studies, to further elucidate these crucial signaling pathways.

scholarly journals Dominant Enhancers of Egfr in Drosophila melanogaster: Genetic Links Between the Notch and Egfr Signaling Pathways

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1139-1153 ◽  
Author(s):  
James V Price ◽  
Edward D Savenye ◽  
David Lum ◽  
Ashton Breitkreutz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Growth Factor Receptor ◽  
Compound Eyes ◽  
Egfr Signaling ◽  
Wing Vein ◽  
Developmental Context ◽  
Epidermal Growth ◽  
Hypomorphic Alleles ◽  
Complex Signaling

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed and F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

scholarly journals Mesenchymal stem cells regulate maintenance of neural stem cells through VEGFR2 and Notch signaling pathways

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S59-S59
Author(s):  
Zhifeng Deng ◽  
Zhumin Liu ◽  
Wei Tu ◽  
Yang Wang ◽  
Yuanlei Lou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathways

scholarly journals Modulation of Bovine Endometrial Cell Receptors and Signaling Pathways as a Nanotherapeutic Exploration against Dairy Cow Postpartum Endometritis

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1516
Author(s):  
Ayodele Olaolu Oladejo ◽  
Yajuan Li ◽  
Xiaohu Wu ◽  
Bereket Habte Imam ◽  
Jie Yang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Signal Transduction Pathway ◽  
Endometrial Cell ◽  
Cell Receptors ◽  
Endometrial Cells ◽  
Microbial Invasion ◽  
Pass Through ◽  
Pro Inflammatory Cytokines

In order to control and prevent bovine endometritis, there is a need to understand the molecular pathogenesis of the infectious disease. Bovine endometrium is usually invaded by a massive mobilization of microorganisms, especially bacteria, during postpartum dairy cows. Several reports have implicated the Gram-negative bacteria in the pathogenesis of bovine endometritis, with information dearth on the potentials of Gram-positive bacteria and their endotoxins. The invasive bacteria and their ligands pass through cellular receptors such as TLRs, NLRs, and biomolecular proteins of cells activate the specific receptors, which spontaneously stimulates cellular signaling pathways like MAPK, NF-kB and sequentially triggers upregulation of pro-inflammatory cytokines. The cascade of inflammatory induction involves a dual signaling pathway; the transcription factor NF-κB is released from its inhibitory molecule and can bind to various inflammatory genes promoter. The MAPK pathways are concomitantly activated, leading to specific phosphorylation of the NF-κB. The provision of detailed information on the molecular pathomechanism of bovine endometritis with the interaction between host endometrial cells and invasive bacteria in this review would widen the gap of exploring the potential of receptors and signal transduction pathways in nanotechnology-based drug delivery system. The nanotherapeutic discovery of endometrial cell receptors, signal transduction pathway, and cell biomolecules inhibitors could be developed for strategic inhibition of infectious signals at the various cell receptors and signal transduction levels, interfering on transcription factors activation and pro-inflammatory cytokines and genes expression, which may significantly protect endometrium against postpartum microbial invasion.

scholarly journals Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Reproductive Tract ◽  
Ovarian Function ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Female Reproductive Tract ◽  
Uterine Receptivity ◽  
Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

Mechanical signal transduction in skeletal muscle growth and adaptation

2005 ◽  
Vol 98 (5) ◽  
pp. 1900-1908 ◽  
Author(s):  
James G. Tidball
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Mechanical Activation ◽  
Signaling Pathways ◽  
Mechanical Stimulation ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Mechanical Signal ◽  
Igf I

The adaptability of skeletal muscle to changes in the mechanical environment has been well characterized at the tissue and system levels, but the mechanisms through which mechanical signals are transduced to chemical signals that influence muscle growth and metabolism remain largely unidentified. However, several findings have suggested that mechanical signal transduction in muscle may occur through signaling pathways that are shared with insulin-like growth factor (IGF)-I. The involvement of IGF-I-mediated signaling for mechanical signal transduction in muscle was originally suggested by the observations that muscle releases IGF-I on mechanical stimulation, that IGF-I is a potent agent for promoting muscle growth and affecting phenotype, and that IGF-I can function as an autocrine hormone in muscle. Accumulating evidence shows that at least two signaling pathways downstream of IGF-I binding can influence muscle growth and adaptation. Signaling via the calcineurin/nuclear factor of activated T-cell pathway has been shown to have a powerful influence on promoting the slow/type I phenotype in muscle but can also increase muscle mass. Neural stimulation of muscle can activate this pathway, although whether neural activation of the pathway can occur independent of mechanical activation or independent of IGF-I-mediated signaling remains to be explored. Signaling via the Akt/mammalian target of rapamycin pathway can also increase muscle growth, and recent findings show that activation of this pathway can occur as a response to mechanical stimulation applied directly to muscle cells, independent of signals derived from other cells. In addition, mechanical activation of mammalian target of rapamycin, Akt, and other downstream signals is apparently independent of autocrine factors, which suggests that activation of the mechanical pathway occurs independent of muscle-mediated IGF-I release.

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