The Expression Levels of Notch-Related Signaling Molecules in Pulmonary Microvascular Endothelial Cells in Bleomycin-Induced Rat Pulmonary Fibrosis

Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, Western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i.e. Notch1, Jagged1, Delta-like ligand 4 (Dll4), and hairy and enhancer of split homolog 1 (Hes1), between a control group treated with intratracheal instillation of saline and a study group treated with intratracheal instillation of BLM solution. Expression levels of the receptor Notch1 and one of its ligands, Jagged1, were upregulated, while the expression levels of the ligand Dll4 and the target molecule of the Notch signaling pathway, Hes1, were downregulated. The differences in protein and mRNA expression levels between the control and study groups were significant (p<0.001). The Jagged1/Notch1 signaling pathway is activated in the pathogenesis of BLM-induced rat pulmonary fibrosis, while the Dll4/Notch1 signaling pathway is inhibited, which inhibits the suppressive effect of Dll4/Notch1 signaling on PMVEC overproliferation, further causing PMVEC dysfunction in cell sprouting and maturation as well as abnormal differentiation of the cell phenotype. Conversely, the down-expression of Hes1 indicates that the Jagged1/Notch1 signaling pathway could be a non-canonical Notch signaling pathway independent of Hes1 activation, which differs from the canonical Dll4/Notch1 signaling pathway.

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Activation of the Notch Signaling Pathway and Cellular Localization of Notch Signaling Molecules in the Spinal Cord of SOD1-G93A ALS Model Mice

Neuroscience ◽

10.1016/j.neuroscience.2020.02.034 ◽

2020 ◽

Vol 432 ◽

pp. 84-93 ◽

Cited By ~ 1

Author(s):

Chong Liu ◽

Dongxiao Li ◽

Cui Lv ◽

Zhisong Gao ◽

Yinkuang Qi ◽

...

Keyword(s):

Spinal Cord ◽

Notch Signaling ◽

Signaling Pathway ◽

Cellular Localization ◽

Notch Signaling Pathway ◽

Signaling Molecules

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Tip60 Histone Acetyltransferase Acts as a Negative Regulator of Notch1 Signaling by Means of Acetylation

Molecular and Cellular Biology ◽

10.1128/mcb.01515-06 ◽

2007 ◽

Vol 27 (18) ◽

pp. 6506-6519 ◽

Cited By ~ 32

Author(s):

Mi-Yeon Kim ◽

Eun-Jung Ann ◽

Jin-Young Kim ◽

Jung-Soon Mo ◽

Ji-Hye Park ◽

...

Keyword(s):

Signaling Pathway ◽

Uv Irradiation ◽

Cell Types ◽

Notch Signaling Pathway ◽

Negative Regulator ◽

Physical Interaction ◽

Notch1 Signaling ◽

Trimeric Complex ◽

A Domains ◽

Notch1 Signaling Pathway

ABSTRACT The Notch signaling pathway appears to perform an important function in a wide variety of organisms and cell types. In our present study, we provide evidence that UV irradiation-induced Tip60 proteins reduced Notch1 activity to a marked degree. Accumulated UV irradiation-induced Tip60 suppresses Notch1 transcriptional activity via the dissociation of the Notch1-IC-CSL complex. The binding between endogenous Tip60 and Notch1-IC in UV radiation-exposed cells was verified in this study by coimmunoprecipitation. Interestingly, the physical interaction of Tip60 with Notch1-IC occurs to a more profound degree in the presence of CSL but does not exist in a trimeric complex. Using Notch1-IC and Tip60 deletion mutants, we also determined that the N terminus, which harbors the RAM domain and seven ankyrin repeats of Notch1-IC, interacts with the zinc finger and acetyl coenzyme A domains of Tip60. Furthermore, here we report that Notch1-IC is a direct target of the acetyltransferase activity of Tip60. Collectively, our data suggest that Tip60 is an inhibitor of the Notch1 signaling pathway and that Tip60-dependent acetylation of Notch1-IC may be relevant to the mechanism by which Tip60 suppresses Notch1 signaling.

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Potential role of the Jagged1/Notch1 signaling pathway in the endothelial-myofibroblast transition during BLM-induced pulmonary fibrosis

Journal of Cellular Physiology ◽

10.1002/jcp.26122 ◽

2017 ◽

Vol 233 (3) ◽

pp. 2451-2463 ◽

Cited By ~ 17

Author(s):

Qian Yin ◽

Weihua Wang ◽

Guangbin Cui ◽

Linfeng Yan ◽

Song Zhang

Keyword(s):

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Potential Role ◽

Notch1 Signaling ◽

Notch1 Signaling Pathway

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Notch Signaling Molecules Activate TGF-βin Rat Mesangial Cells under High Glucose Conditions

Journal of Diabetes Research ◽

10.1155/2013/979702 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Li Liu ◽

Chenlin Gao ◽

Guo Chen ◽

Xia Li ◽

Jia Li ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Notch Signaling ◽

Signaling Pathway ◽

High Glucose ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Notch Pathway ◽

Notch Signaling Pathway ◽

Signaling Molecules ◽

Dependent Manner

The involvement of the Notch signaling pathway in the cellular differentiation of the mammalian kidney is established. Recently, the dysregulation of Notch signaling molecules has been identified in acute and chronic renal injuries, fibrosis models, and diabetic kidney biopsies. The canonical Notch ligand , Jagged1, is upregulated in a transforming growth factor-beta- (TGF-β-) dependent manner during chronic kidney disease. TGF-β, a central mediator of renal fibrosis, also is a major contributor to the development of diabetic nephropathy. To explore the roles and possible mechanisms of Notch signaling molecules in the pathogenesis of diabetic nephropathy, we exposed cultured rat mesangial cells to aγ-secretase inhibitor (DAPT) or high glucose and measured the expression of Notch signaling molecules and the fibrosis index. Notch pathway-related molecules, TGF-β, and fibronectin increased with exposure to high glucose and decreased with DAPT treatment. Our results suggest that the Notch signaling pathway may precipitate diabetic nephropathy via TGF-βactivation.

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

Cellular Physiology and Biochemistry ◽

10.1159/000491539 ◽

2018 ◽

Vol 47 (6) ◽

pp. 2291-2306 ◽

Cited By ~ 24

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.

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Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.4687 ◽

2020 ◽

Author(s):

Zhong Fang-Fang ◽

Yang You ◽

Liu Wen-Jun

Keyword(s):

T Cell ◽

Signaling Pathway ◽

Acute Lymphocytic Leukemia ◽

Childhood Leukemia ◽

Notch Signaling Pathway ◽

Lymphocytic Leukemia ◽

Activating Mutations ◽

Notch1 Signaling ◽

Child Patients ◽

Notch1 Signaling Pathway

Childhood leukemia is a cancer seriously threatening children’s life in China. The treatment of T-cell acute lymphocytic leukemia (T-ALL) is extremely difficult due to its early infiltration, poor sensitivity to chemotherapy, and susceptibility to drug resistance. At the same time, the traditional intensive chemotherapy regimens cause great damage to children, so it is highly important to search for the targeted drugs and develop precise individualized treatment of child patients. The Notch signaling pathway is involved the pathogenesis of T-ALL, and there are activating mutations in the NOTCH1 gene in more than 50% of human T-ALLs. In this review, we summarize the progress in research on T-ALL and Notch1 signaling pathway inhibitors, so as to provide a theoretical basis for the clinical treatment of T-ALL.

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