scholarly journals Jagged2-γδT17 is Regulated by Mycobacterium Vaccae in Asthmatic Mice

2021 ◽  
Author(s):  
Yi-En Yao ◽  
Qi-Xiang Sun ◽  
Jing-Hong Zhang ◽  
Jian-Lin Huang ◽  
Si-Yue Xu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Notch Signaling ◽  
Airway Inflammation ◽  
Signaling Pathway ◽  
Signal Transduction Pathway ◽  
Notch Signaling Pathway ◽  
Control Group ◽  
Transduction Pathway ◽  
Γδt Cells ◽  
Mycobacterium Vaccae

Abstract Background: Mycobacterium vaccae nebulization imparted protective effect against asthma in a mouse model. The Jagged2-γδT17 signal transduction pathway plays an important role in bronchial asthma. However, the effect of M. vaccae nebulization on the Jagged2-γδT17 signal transduction pathway in mouse models of asthma remains unclear. Methods: In total, 30 female C57 mice were randomized to normal control (group a), asthma control (group b), M. vaccae nebulization prevention,and M. vaccae nebulization treatment (group d) groups. Asthma mice models were created using ovalbumin (OVA). The Notch signaling pathway was blocked by DAPT inhibitors. Airway hyperreactivity (AHR) was measured by noninvasive lung function tests. Histopathological analyses using blue-periodic acid Schiff along with hematoxylin and eosin were performed. Immunohistochemistry, immunofluorescence, and a Western blotting assay allowed for the detection of lung protein expressions, while spleen expressions of IL-17+γδT+ cytokines were assessed with FLOW cytometry. One-way analysis of variance for within-group comparisons, the least significant difference t-test or Student-Newman-Keuls test for intergroup comparisons, and the nonparametric rank sum test for analysis of airway inflammation scores were used in the study. Results: Asthmatic mice models demonstrated downregulated Notch signaling pathway activation and decreased γδT cells and IL-17 cytokine secretion. There was also increased Jagged2 protein expression which correlated positively with γδT+IL-17+ secretion. In asthmatic mice, the expressions of Jagged2 and γδT17, along with airway inflammation and airway reactivity, were all decreased after M. vaccae exposure (p<0.05). Conclusion: The Notch signaling pathway contributed towards asthma initiation and progression by facilitating γδT cells and IL-17 cytokines production. Inhaled M. vaccae led to a significant decrease in Jagged2 and γδT17 expressions in asthmatic mice, indicating its utility in asthma prevention.

Targeting the JAK/STAT Signaling Pathway for Breast Cancer.

2020 ◽  
Vol 28 ◽  
Author(s):  
Fei Shao ◽  
Xiaonan Pang ◽  
Gyeong Hun Baeg
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Signaling Pathway ◽  
Signal Transduction Pathway ◽  
Breast Cancer Treatment ◽  
Review Article ◽  
Transduction Pathway ◽  
Inhibitory Effects ◽  
Stat Proteins ◽  
Stat Signaling

Abstract:: Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, includ-ing radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibi-tors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.

scholarly journals Notch Signaling Pathway Is Involved in bFGF-Induced Corneal Lymphangiogenesis and Hemangiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Fang Xie ◽  
Xue Zhang ◽  
Wenting Luo ◽  
Hongyan Ge ◽  
Dawei Sun ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Expression Level ◽  
Control Group ◽  
Fluorescence Signal ◽  
Mrna And Protein Expression ◽  
Corneal Lymphangiogenesis

Background. Notch/Dll4 involvement in cornea neovascularization (CRNV) and lymphangiogenesis is unclear. This study aimed to explore the role of notch signaling in basic fibroblast growth factor- (bFGF-) induced corneal lymphangiogenesis and hemangiogenesis. Methods. Corneal stroma of C57BL/6 mice was implanted with bFGF- or phosphate-buffered saline- (PBS-) soaked pellets. Corneal lymphangiogenesis and neovascularization were evaluated by immunofluorescence. Vascular endothelial growth factor-A (VEGF-A), Delta-like ligand 4 (Dll4), and Notch1 mRNA and protein expression were examined on days 1, 3, 7, and 14 by real-time polymerase chain reaction and western blot. Corneal cells were treated with ranibizumab, dexamethasone, and γ-secretase inhibitor (GSI). Microspheres were used to evaluate corneal hemangiogenesis in vivo. Results. Corneal hemangiogenesis reached its peak on day 7 after bFGF implantation, and corneal lymphangiogenesis was significantly higher on day 7 and 14, compared with PBS. mRNA and protein expression of VEGF-A, Dll4, and Notch1 were higher in bFGF-induced animal models compared with controls. Corneal hemangiogenesis and lymphangiogenesis decreased after 7 days of ranibizumab or dexamethasone treatment. After adding GSI for 24 h in bFGF-induced cells, the expression of Notch1 and Dll4 were downregulated compared with that in the control group whereas the expression level of VEGF-A was upregulated. Fluorescent particle number was higher in the GSI group. Ranibizumab and dexamethasone decreased the fluorescence signal. Conclusion. The notch signaling pathway plays a role in regulating VEGF expression, affecting corneal lymphangiogenesis and hemangiogenesis in mice. The molecular imaging probe technique can visualize the changes in the VEGF-A expression level of corneal limbus hemangiogenesis.

The Activation of Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signal Transduction Pathway on Invasive Growth of Breast Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 1005-1009
Author(s):  
Wei Ma ◽  
Lie Ma ◽  
Shaoqi Yang ◽  
Kai Wang
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cell Invasion ◽  
Signal Transduction Pathway ◽  
Control Group ◽  
Transduction Pathway ◽  
Erk Mapk ◽  
Proliferation Activity ◽  
Proliferation And Invasion ◽  
Mcf 7

ERK/MAPK signal transduction pathway participates in occurrence and progression of breast cancer. This study utilized epidermal growth factor (EGF) and ERK antagonist PD98059 to analyze ERK/MAPK signal's role in breast cancer cells. Breast cancer MCF-7 cell line was separated into control group, EGF group, PD98059 group and EGF+ PD98059 group. Cell proliferation activity was assessed by MTT, whilst TUNEL was to describe cell apoptosis. Transwell assay was employed for cell invasion and migration. Protein expression of ERK1/2 and p-ERK1/2. Compared to control group, EGF treatment elevated cell proliferation or invasion/migration and decreased apoptosis at 6 h, 12 h and 24 h. PD98059 treatment decreased proliferation activity or cell invasion/migration, and enhanced apoptosis. Treatment of EGF plus PD98059 further decreased proliferation and invasion/migration compared to EGF group, but with higher level than PD98059 group (p < 0 05). EGF treatment elevated ERK1/2 and pERK1/2, PD98059 group had lower ERK1/2 or pERK1/2 expression, whilst EGF plus PD98059 treatment further decreased ERK1/2 and pERK1/2 expression (p < 0 05). EGF can regulate proliferation and invasion of breast cancer MCF-7 cells via ERK/MAPK signaling.

scholarly journals Astragalus Polysaccharide RAP Induces Macrophage Phenotype Polarization to M1 via the Notch Signaling Pathway

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2016 ◽  
Author(s):  
Wei Wei ◽  
Zhi-Peng Li ◽  
Zhao-Xiang Bian ◽  
Quan-Bin Han
Keyword(s):  
Tumor Growth ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Macrophage Phenotype ◽  
Astragalus Polysaccharide ◽  
M1 Phenotype

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells’ cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage’s polarization to M1 phenotype via the Notch signaling pathway.

scholarly journals Prediction of protein architectures involved in the signaling-pathway initiating sporulation in Firmicutes

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Paola Martinez-Amador ◽  
Nori Castañeda ◽  
Antonio Loza ◽  
Lizeth Soto ◽  
Enrique Merino ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signaling Pathway ◽  
Signal Transduction Pathway ◽  
Comparative Genomic ◽  
Transduction Pathway ◽  
Genomic Context ◽  
Query Gene ◽  
Data Description ◽  
Signal Transduction Cascade ◽  
Manual Curation

Abstract Objectives Like many other proteins, those belonging to the signal transduction cascade initiating sporulation (Spo0 pathway) have conserved protein domains (Capra and Laub in Annu Rev Microbiol 66:325–47, 2012). Improvements in bioinformatics applications to discover proteins involved in the initiation of the sporulating cascade in newly sequenced genomes is an important task that requires rigorous comparative genomic methods and manual curation to identify endospore-forming bacteria. This note aims to present a collection of predicted proteins involved in the Spo0 pathway found in the proteomes of fully sequenced and manually curated endospore-forming Firmicutes species. This collection may serve as a guide to conduct future experiments in endospore formers in genomic and metagenomic projects. Data description Similar to the report of Davidson et al. (PLoS Genet 14:1–33, 2018), we used Pfam profiles (El-Gebali et al. in Nucleic Acids Res 47:D427–32, 2019) defining each protein and the genomic context surrounding the query gene to predict probable orthologs of the Spo0 pathway in Firmicutes. We present in this note a collection of 325 Firmicutes species organized by phylogenetic class and classified as spore formers, non-spore formers or unknown spore phenotype based on published literature, for which we predicted probable orthologs defining the signal transduction pathway initiating sporulation.

scholarly journals Myostatin Signals through a Transforming Growth Factor β-Like Signaling Pathway To Block Adipogenesis

2003 ◽  
Vol 23 (20) ◽  
pp. 7230-7242 ◽  
Author(s):  
A. Rebbapragada ◽  
H. Benchabane ◽  
J. L. Wrana ◽  
A. J. Celeste ◽  
L. Attisano
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Signal Transduction Pathway ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Type I ◽  
Type Ii ◽  
Transduction Pathway

ABSTRACT Myostatin, a transforming growth factor β (TGF-β) family member, is a potent negative regulator of skeletal muscle growth. In this study we characterized the myostatin signal transduction pathway and examined its effect on bone morphogenetic protein (BMP)-induced adipogenesis. While both BMP7 and BMP2 activated transcription from the BMP-responsive I-BRE-Lux reporter and induced adipogenic differentiation, myostatin inhibited BMP7- but not BMP2-mediated responses. To dissect the molecular mechanism of this antagonism, we characterized the myostatin signal transduction pathway. We showed that myostatin binds the type II Ser/Thr kinase receptor. ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (TβRI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-β-like signaling pathway. We demonstrated that myostatin prevents BMP7 but not BMP2 binding to its receptors and that BMP7-induced heteromeric receptor complex formation is blocked by competition for the common type II receptor, ActRIIB. Thus, our results reveal a strikingly specific antagonism of BMP7-mediated processes by myostatin and suggest that myostatin is an important regulator of adipogenesis.

scholarly journals Effect of NTN and Lmx1α on the Notch Signaling Pathway during the Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Dopaminergic Neuron-Like Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jinhua Zhang ◽  
Bo Yang ◽  
Lilin Luo ◽  
Linhui Li ◽  
Xuantao Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Dopaminergic Neuron ◽  
Notch Signaling Pathway ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells

Human bone marrow mesenchymal stem cells (h-BMSCs) have the potential to differentiate into dopaminergic neuron-like cells to treat Parkinson’s disease. The Notch signaling pathway has been implicated in the regulation of cell fate decisions such as differentiation of BMSCs. This study investigated changes in the expression of Notch-related genes in the differentiation of BMSCs in vitro into dopaminergic (DA) neuron-like cells. BMSCs transfected with empty lentiviral vectors served as the control group and those transfected with NTN and Lmx1α recombinant lentiviral vectors served as the experimental group. After induction and culture of NTN and Lmx1α-transfected h-BMSCs for 21 days, the cells exhibited features of dopaminergic neuron-like cells, which were observed by transmission and scanning electron microscopy and verified by immunofluorescence of tyrosine hydroxylase (TH) and dopamine transporter (DAT). These induced cells could secrete dopamine and had basic action potentials. Expression of the neural stem cell (NSC) markers, including octamer-binding protein (Oct4), paired box gene 6 (Pax6), and sex determining region Y-box 1 (SOX1), increased on day 14 of induction and decreased on day 21 of induction during differentiation. The human Notch signaling pathway PCR array showed a differential expression of Notch-related genes during the differentiation of h-BMSCs into DA neuron-like cells in vitro relative to that in the control group. In conclusion, h-BMSCs overexpressing NTN and Lmx1α can successfully be induced to differentiate into dopaminergic neuron-like cells with a neuronal phenotype exhibiting fundamental biological functions in vitro, and NTN and Lmx1α may affect the expression of Notch-related genes during differentiation.

scholarly journals LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

2018 ◽  
Vol 47 (6) ◽  
pp. 2291-2306 ◽  
Author(s):  
Yu Wang ◽  
Tian-Bao Luo ◽  
Long Liu ◽  
Zhi-Qiang Cui
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Activity ◽  
Notch Signaling Pathway ◽  
Control Group ◽  
Expression Levels ◽  
Proliferation And Differentiation ◽  
Expression Rate ◽  
Non Coding Rnas ◽  
Sirna Group

Background/Aims: Osteoporosis is a commonly occurring condition marked by a loss of bone density. Previous evidence has highlighted the roles played by microRNAs as potential treatment tools for the disease. At present, the influence of long non-coding RNAs (lncRNAs) on the progression of osteoporosis remains largely unclear. Thus, an investigation was conducted into the target relationship between LINC00311, which has been reported to be highly expressed in osteoporosis, and delta-like 3 (DLL3), which is involved in the Notch signaling pathway, in connection with a series of bioinformatic methods. An osteoporotic rat model was established by means of ovariectomy (OVX) to evaluate the influence exerted by DLL3-binding LINC00311 on osteoclasts through the Notch signaling pathway. Methods: Osteoclasts were extracted from osteoporotic rats and transfected with the LINC00311-vector, shRNA-LINC00311, Notch activator, or a combination of the Notch activator and LINC00311-vector. Western blotting and RT-qPCR techniques were applied to determine the expression levels of LINC00311, DLL3, Notch1, Notch2, Jagged1, Hes-1 and TRAP in tissues and cells, while cell activity was detected by MTT assay. The cell cycle as well as the rate of apoptosis was detected by flow cytometry. The successfully established osteoporotic rats were designated into the OVX-siRNA, OVX-LINC00311 and OVX-control groups to observe the effects of LINC00311 on the proliferation and differentiation of osteoclasts. Results: Cells transfected with the LINC00311-vector exhibited increased expression levels of Notch2 and TRPA as well as increased cell activity, while decreased expression levels of DLL3, Notch1, Jagged1 and Hes-1, along with a decreased cell apoptosis rate, were observed. The opposite tendencies of these parameters were observed in the cells treated with shRNA-LINC00311. A key observation was made when the Notch signaling pathway was activated, in that the cell activity was decreased while the rate of apoptosis increased. In comparison with the OVX-control group, the expression levels of LINC00311, Notch2 and TRAP as well as the positive expression rate of TRAP all exhibited reductions, while those of DLL3, Jagged1 and Notch1 were elevated in the OVX-siRNA group. Compared with those in the sham group, in the OVX-control and OVX-LINC00311 groups, LINC00311 and the expression levels of Notch2 and TRAP were increased; however, decreased levels of DLL3, Jagged1 and Notch1 were noted. Conclusions: Taken together, the key findings of the present study suggest that LINC00311 induces proliferation and inhibits apoptosis of osteoclasts via the regulation of the Notch signaling pathway by inhibiting DLL3 expression, ultimately demonstrating that LINC00311 and its target gene DLL3 may serve as independent factors in cases of osteoporosis.

Sign in / Sign up

Export Citation Format

Share Document