scholarly journals Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

2017 ◽  
Vol 42 (2) ◽  
pp. 743-752 ◽  
Author(s):  
Ren-Jun Peng ◽  
Bing Jiang ◽  
Xi-Ping Ding ◽  
He Huang ◽  
Yi-Wei Liao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Rat Model ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Tnf Α ◽  
Cord Injury ◽  
Mrna And Protein Expression ◽  
Gsk 3Β

Aim: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. Methods: The rat model of SCI was established using Allen’s method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of β-catenin, Wnt3a, GSK-3β and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. Results: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the β-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3β and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.

Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

scholarly journals Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

2017 ◽  
Vol 44 (1) ◽  
pp. 85-98 ◽  
Author(s):  
Xiao-Lei Wang ◽  
Chun-Mei Qiao ◽  
Jiong-Ou Liu ◽  
Chun-Yang Li
Keyword(s):  
Ischemic Stroke ◽  
Protein Expression ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuronal Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Mrna And Protein Expression

Background: The present study aims to investigate the protective effects of the SOCS1-JAK2-STAT3 signaling pathway on neurons in a rat model of ischemic stroke. Methods: Our study was conducted using an ischemic stroke rat model. After the microglia were extracted, 40 neonatal Sprague-Dawley (SD) rats were assigned into the blank, AG490, model and negative control (NC) groups. The neurological function of all the rats was evaluated. Histopathological changes were observed. qRT-PCR and western blotting were applied to measure the expression of genes and proteins in the SOCS1-JAK2-STAT3 signaling pathway and related to apoptosis. The TUNEL assay was conducted to calculate the cellular morphology and apoptosis of neuronal cells. Cell viability was detected using the MTT assay. In addition, immunoassays were used to measure the content of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) as well as the levels of oxidative stress. Results: Compared with the blank group, the model and NC groups showed higher neurological function scores—the cytoplasm of the neurons were cavitated, the organelles were reduced with unclear margins, some of the neurons were necrotic, and apoptosis was increased. In addition, the NC and model groups exhibited decreased cell viability, lower mRNA and protein expression of SOCS1 SOCS3 and bcl-2 and reduced SOD and GSH levels but higher mRNA and protein expression levels of AK2, STAT3,Bax and caspase-3 as well as increased protein expression of P-JAK2, P-STAT3 and activated caspase-3 (c-caspase-3). Moreover, the MDA levels were up-regulated in the NC and model groups. In contrast, opposing trends were found in the AG490 group compared with the NC and model groups. Conclusion: These data demonstrate that inhibiting the SOCS1-JAK2-STAT3 signaling pathway can reduce the loss of nerve function and apoptosis of neuronal cells, which provides a new target for the clinical treatment of ischemic stroke.

Investigate the Effect of miR-22 on the Apoptosis of Coronary Heart Disease Cells Through the Wnt-1 Pathway Based on Nano-Silica-Induced Rat Models

2021 ◽  
Vol 21 (2) ◽  
pp. 1338-1344
Author(s):  
Fangjing Wei ◽  
Baojun Ren ◽  
Wei Han ◽  
Hong Guan ◽  
Guoqiang Jing ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Myocardial Cell ◽  
Control Group ◽  
Myocardial Cells ◽  
Nano Silica ◽  
Rat Cardiomyocytes

In this paper, by examining the toxicity of nano-silica to coronary heart disease cells, we explored the apoptosis of rat myocardial cells induced by nano-silica, and explored the effect of apoptosis on cells during the process of myocardial cytotoxicity induced by nano-silica. This article selects rat cardiomyocytes as the research object and conducts a group control experiment. A control group is set up with cells that are not stained with nano-silica. Different concentrations of nanosilica suspensions are applied to rat cells and detected by CCK-8 method. Cell survival rate after exposure to different concentrations of cells is used to determine the most stable exposure time and concentration. We used flow cytometry to detect intracellular reactive oxygen species and apoptotic rates, and used Western Blot to detect the expression of proteins that affect apoptosis. Finally, we investigated the effect of the Wnt signaling pathway on coronary heart disease. The Wnt signaling pathway regulates the development of the heart and blood vessels. In the treatment of cardiovascular disease, this pathway will be activated again to play a regulatory role. We conclude that nano-silica can induce cytotoxicity in rat myocardial cells through the Wnt-1 pathway, and nanosilica can induce myocardial cell apoptosis through the Wnt-1 pathway.

scholarly journals Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin

Oncogene ◽  
2007 ◽  
Vol 27 (3) ◽  
pp. 274-284 ◽  
Author(s):  
K Haraguchi ◽  
M Ohsugi ◽  
Y Abe ◽  
K Semba ◽  
T Akiyama ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Gsk 3Β

Wnt/β-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy

2005 ◽  
Vol 289 (4) ◽  
pp. C853-C859 ◽  
Author(s):  
Dustin D. Armstrong ◽  
Karyn A. Esser
Keyword(s):  
Skeletal Muscle ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Muscle Hypertrophy ◽  
Glycogen Synthase ◽  
Wnt Signaling Pathway ◽  
Growth Control ◽  
Skeletal Muscle Hypertrophy ◽  
Study Results ◽  
Gsk 3Β

β-Catenin is a transcriptional activator shown to regulate the embryonic, postnatal, and oncogenic growth of many tissues. In most research to date, β-catenin activation has been the unique downstream function of the Wnt signaling pathway. However, in the heart, a Wnt-independent mechanism involving Akt-mediated phosphorylation of glycogen synthase kinase (GSK)-3β was recently shown to activate β-catenin and regulate cardiomyocyte growth. In this study, results have identified the activation of the Wnt/β-catenin pathway during hypertrophy of mechanically overloaded skeletal muscle. Significant increases in β-catenin were determined during skeletal muscle hypertrophy. In addition, the Wnt receptor, mFrizzled (mFzd)-1, the signaling mediator disheveled-1, and the transcriptional co-activator, lymphocyte enhancement factor (Lef)-1, are all increased during hypertrophy of the overloaded mouse plantaris muscle. Experiments also determined an increased association between GSK-3β and the inhibitory frequently rearranged in advanced T cell-1 protein with no increase in GSK-3β phosphorylation (Ser9). Finally, skeletal muscle overload resulted in increased nuclear β-catenin/Lef-1 expression and induction of the transcriptional targets c-Myc, cyclin D1, and paired-like homeodomain transcription factor 2. Thus this study provides the first evidence that the Wnt signaling pathway induces β-catenin/Lef-1 activation of growth-control genes during overload induced skeletal muscle hypertrophy.

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.

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