Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway

2016 ◽  
Vol 44 (01) ◽  
pp. 103-117 ◽  
Author(s):  
Yu-Lian Zhang ◽  
Zhen Zhou ◽  
Wen-Wen Han ◽  
Lin-Lin Zhang ◽  
Wan-Shan Song ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Cell Model ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Regulated Expression ◽  
Stat Signaling

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

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 Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Min Cai ◽  
Rui Shen ◽  
Lei Song ◽  
Minjie Lu ◽  
Jianguang Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signal Transduction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Glucose Metabolism ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Pet Ct ◽  
Marrow Mesenchymal Stem Cells

Abstract Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

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.

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.

The Wnt Signal Transduction Pathway in Stem Cells and Cancer Cells: Influence on Cellular Invasion

2007 ◽  
Vol 3 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Peter Neth ◽  
Christian Ries ◽  
Marisa Karow ◽  
Virginia Egea ◽  
Matthias Ilmer ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cells ◽  
Cancer Cells ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cellular Invasion ◽  
Wnt Signal
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