Notch signaling pathway is a main pathway through cell-cell interactions, which regulates the programmed cell death, cellular proliferation and differentiation in multiple cell systems, and also is an important signaling pathway to modulate the balance between proliferation and differentiation in hematopoietic environment, and is related with the incidence of multiple hematologic malignancies. Multiple myeloma (MM) is malignant in B cell lineage and characterized by clonal proliferative plasma cells. It is very difficult to cure MM patients with a low proliferation rate of the MM cell and drug resistance to the standard dosage of chemotherapy. In recent years, research has shown that in the malignant plasma cells of the patients with multiple myeloma (MM) and the cell lines, but not in normal plasma cells or tumor cells from patients with other malignancies, the Notch ligand Jagged2 was found to be overexpressed. Jagged2 can induce stromal cells to secrete IL-6, VEGF and IGF-1. Notch activation can interact with NF-kappaB and C-myc to promote the proliferation and to inhibit the apoptosis of MM cells, showing in the relationship between the incidence of myeloma and drug resistance. Inhibition of the Notch signaling pathway may induce the apoptosis of MM cells and enhance the effect of chemotherapy. Study indicated that the specific inhibition of Notch signaling by treatment with a gamma-secretase inhibitor (GSI) alone, a specific pharmacologic inhibitor of Notch signaling, induces the apoptosis of myeloma cells and improves sensitivity of myeloma cell to chemotherapy when combined. In this article the composition of Notch signalling pathway, the mechanism of Notch signalling pathway and the relation of Notch signalling pathway to multiple myeloma were reviewed.
Humans ; Multiple Myeloma ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction

Humans ; Psoriasis ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction

The occurrence and development of many tumors all relate with abnormal expression of the Notch receptor. The role of different Notch receptors may be different, even contrary in different tissues at different stages of tumor development, as well as in the same system tumors. Notch signaling pathway plays an important role in cell proliferation, differentiation, apoptosis and tumor angiogenesis, and is as a meeting point for many important cell signaling pathway. Angiogenesis is regulated by complex interactions of multiple activators and inhibitors. Vascular endothelial growth factor (VEGF) and Notch signaling pathway are involved in such process. Many studies have confirmed that Notch signaling pathway plays a key role in the embryonic development and tumour angiogenesis. Recent studies have also revealed that Notch signaling pathway has many potential drug targets. Based on study of Notch signaling pathway and its molecular mechanism of leukemia, to design drugs effecting these targets to block and activate Notch signaling pathway for therapy of leukemia and angiogenesis diseases has a broad application prospects. This review summarises the components of Notch signaling pathway and the role of Notch signaling pathway in occurrence of leukemia and angiogenesis.
Animals ; Humans ; Leukemia ; metabolism ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology ; Receptors, Notch ; metabolism ; Signal Transduction

Macrophage as a crucial component of innate immunity, plays an important role in inflammation and infection immunity. Notch signal pathway is a highly conserved pathway, which regulates cellular fate and participates in numerous pathological processes. At present, a lot of literature has confirmed the role of Notch signaling in regulating the differentiation, activation and metabolism of macrophage during inflammation and infection. This review focuses on how Notch signaling promotes macrophage pro-inflammatory and anti-infective immune function in different inflammatory and infectious diseases. In this regulation, Notch signaling interact with TLR signaling in macrophages or inflammatory-related cytokines including IL-6, IL-12, and TNF-α. Additionally, the potential application and challenges of Notch signaling as a therapeutic target against inflammation and infectious diseases are also discussed.
Humans ; Signal Transduction ; Macrophages ; Cytokines/metabolism* ; Inflammation/metabolism* ; Communicable Diseases ; Receptors, Notch/metabolism*

The study was aimed to investigate the expression of Notch signal molecules in human lymphoma cells and its significance. Raji, Maver, Z138 and Jurkat cell lines were used in the study. RT-PCR was used to determine the expression of Notch signaling molecules in these lymphoma cells. Flow cytometry was used to detect the apoptosis and cell-cycle of the lymphoma cells induced by different concentrations of gamma secretase inhibitor DAPT. CCK-8 was used to detect the proliferation of the lymphoma cells treated by DAPT. The results showed that the expression of Notch molecules in the four cell lines was different. Notch1 and Notch2 were found to be expressed in the four lymphoma cell lines, Notch3 predominantly expressed in Jurkat cells, Notch4 only expressed in Raji cells weakly and Hes1 only expressed in Raji and Jurkat cells. Treatment with DAPT could increase the apoptosis ratio of Raji and Jurkat cells. Besides, DAPT could significantly inhibit the proliferation of Raji and Jurkat cells by inducing the cell cycle arrest in G(1) phase, but the effect of DAPT on Maver and Z138 cells was not obvious. The activity of Notch pathway could be inhibited by DAPT treatment through down-regulating the expression of Notch target gene Hes1. It is concluded that the abnormal expression and activation of Notch signal pathway play an important role in the proliferation of lymphoma cells. Notch may be likely a new target for the therapy of lymphoma.
Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Humans ; Lymphoma ; metabolism ; pathology ; Receptors, Notch ; metabolism ; Signal Transduction

Mesenchymal stem cell (MSC) is an adult stem cell which has the multipotential differentiation ability. In vitro experiments demonstrated that MSC is able to differentiate into various lineage cells including bone, cartilage, fat, and muscle cells. In addition, MSC has also been shown to differentiate into neural precursors, cardiomyocytes, liver cells, and possible other cell types. The Notch pathway is a highly conserved signaling mechanism involved in many processes determining cell fate during the animal development, and plays an important role in the regulation of cell differentiation, proliferation and apoptosis. Notch ligands and receptors are both transmembrane proteins, and suggest that Notch-mediated cellular interaction is an important way in cell to cell communication. Studies of Notch function provide evidence that Notch signaling affects various differentiation capabilities of MSC. In this review, the roles of Notch signaling in differentiation of MSC are summarized.
Animals ; Cell Differentiation ; Drosophila ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction

Ex vivo expansion of hematopoietic progenitor cells (HPCs) is valuable for clinical application, however, traditional ex vivo culture negatively affects long-term hematopoietic reconstitution ability. In the hematopoietic system, the expression of Notch receptors and their ligands has been widely reported. Active Notch signal inhibits the differentiation of HSCs while promotes their expansion, suggesting that ex vivo expansion of hematopoietic progenitor cells could be enhanced by manipulating Notch signal pathways. In this article the Notch signal pathways, Notch signal and maintenance of hematopoietic progenitor cells, Notch signal and expansion of hematopoietic progenitor cells and molecular mechanism of Notch signal maintaining undifferentiation of hematopoietic progenitor cells were reviewed.
Animals ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Receptors, Notch ; metabolism ; Signal Transduction

Notch signaling pathway is a highly conserved signaling pathway in the process of evolution. It is composed of three parts: Notch receptor, ligand and effector molecules responsible for intracellular signal transduction. It plays an important role in cell proliferation, differentiation, development, migration, apoptosis and other processes, and has a regulatory effect on tissue homeostasis and homeostasis. Mitochondria are the sites of oxidative metabolism in eukaryotes, where sugars, fats and proteins are finally oxidized to release energy. In recent years, the regulation of Notch signaling pathway on mitochondrial energy metabolism has attracted more and more attention. A large number of data have shown that Notch signaling pathway has a significant effect on mitochondrial energy metabolism, but the relationship between Notch signaling pathway and mitochondrial energy metabolism needs to be specifically and systematically discussed. In this paper, the relationship between Notch signaling pathway and mitochondrial energy metabolism is reviewed, in order to improve the understanding of them and provide new ideas for the treatment of related diseases.
Signal Transduction/physiology* ; Mitochondria ; Receptors, Notch/metabolism* ; Cell Differentiation/physiology* ; Energy Metabolism

Animals ; Humans ; Liver ; growth & development ; Liver Diseases ; Receptors, Notch ; metabolism ; Signal Transduction

OBJECTIVETo study the expressions of Notch1-4 gene in human keloid-derived mesenchymal-like stem cells, and to explore the Notch signaling pathway's role in the formation of keloid.

METHODSKeloid samples were collected to harvest human keloid-derived mesenchymal-like stem cells through two-step enzymatic dissociation method. By flow cytometry, cell phenotype of primary and P3 generation were analyzed. By immunocytochemistry, the expressions of Oct4, vimentin and CK19 were examined. Keloid-derived mesenchymal-like stem cells were induced into osteoblasts in vitro and calcium deposition was detected by Alizarin red S stain. Realtime polymerase chain reaction (RT-PCR) was used to detect the expressions of Notch1-4 mRNA in keloid-derived mesenchymal-like stem cells.

RESULTSFlow cytometry showed that keloid-derived mesenchymal-like stem cells of primary and P3 generation highly expressed CD29, CD44, CD90 from the typical MSC phenotype marker, but they failed to express HSC phenotype markers, such as CD34 and CD45. The results of immunocytochemistry showed that Oct4 from pluripotent stem cell markers and vimentin from mesenchymal cell markers was positive and CK19 from epithelial cell markers was negative. After induced differentiation into osteoblasts in vitro after 21 day, calcium nodules could be seen clearly; Notch1-4 gene were expressed in keloid-derived mesenchymal-like stem cells through RT-PCR. The relative quantitative of Notch2, Notch3 gene were higher than Notch1, Notch4 gene (P < 0.05).

CONCLUSIONSThe expression difference of different subtypes from Notch gene in human keloid-derived mesenchymal-like stem ceils may be related to self-renewal, proliferation, differentiation, and participate in the formation of keloid.

Adolescent ; Cells, Cultured ; Child ; Female ; Humans ; Keloid ; metabolism ; pathology ; Male ; Mesenchymal Stromal Cells ; metabolism ; Receptors, Notch ; metabolism