Notch signaling pathway in infectious diseases: role in the regulation of immune response

2021 ◽  
Vol 70 (3) ◽  
pp. 261-274
Author(s):  
Ricardo Cardoso Castro ◽  
Relber Aguiar Gonçales ◽  
Fabiana Albani Zambuzi ◽  
Fabiani Gai Frantz
2013 ◽  
Vol 13 (9) ◽  
pp. 957-962 ◽  
Author(s):  
Yumei Li ◽  
Jia Ma ◽  
Xiujuan Qian ◽  
Qiong Wu ◽  
Jun Xia ◽  
...  

Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mohd Saeed ◽  
Irfan Ahmad ◽  
Irfan A. Ansari

Background: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4′,6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7’-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.


Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1264-1273 ◽  
Author(s):  
Melanie G. Cornejo ◽  
Vinciane Mabialah ◽  
Stephen M. Sykes ◽  
Tulasi Khandan ◽  
Cristina Lo Celso ◽  
...  

Abstract The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masaharu Yoshihara ◽  
Teppei Nishino ◽  
Manoj Kumar Yadav ◽  
Akihiro Kuno ◽  
Takeshi Nagata ◽  
...  

Abstract Objective The Delta-Notch signaling pathway induces fine-grained patterns of differentiation from initially homogeneous progenitor cells in many biological contexts, including Drosophila bristle formation, where mathematical modeling reportedly suggests the importance of production rate of the components of this signaling pathway. In contrast, the epithelial differentiation of bile ducts in the developing liver is unique in that it occurs around the portal vein cells, which express extremely high amounts of Delta ligands and act as a disturbance for the amount of Delta ligands in the field by affecting the expression levels of downstream target genes in the cells nearby. In the present study, we mathematically examined the dynamics of the Delta-Notch signaling pathway components in disturbance-driven biliary differentiation, using the model for fine-grained patterns of differentiation. Results A portal vein cell induced a high Notch signal in its neighboring cells, which corresponded to epithelial differentiation, depending on the production rates of Delta ligands and Notch receptors. In addition, this epithelial differentiation tended to occur in conditions where fine-grained patterning was reported to be lacking. These results highlighted the potential importance of the stability towards homogeneity determined by the production rates in Delta ligands and Notch receptors, in a disturbance-dependent epithelial differentiation.


Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1989-1997 ◽  
Author(s):  
Kyle Niessen ◽  
Gu Zhang ◽  
John Brady Ridgway ◽  
Hao Chen ◽  
Ganesh Kolumam ◽  
...  

Abstract The Notch signaling pathway plays a fundamental role during blood vessel development. Notch signaling regulates blood vessel morphogenesis by promoting arterial endothelial differentiation and pro-viding spatial and temporal control over “tip cell” phenotype during angiogenic sprouting. Components of the Notch signaling pathway have emerged as potential regulators of lymphatic development, joining the increasing examples of blood vessel regulators that are also involved in lymphatic development. However, in mammals a role for the Notch signaling pathway during lymphatic development remains to be demonstrated. In this report, we show that blockade of Notch1 and Dll4, with specific function-blocking antibodies, results in defective postnatal lymphatic development in mice. Mechanistically, Notch1-Dll4 blockade is associated with down-regulation of EphrinB2 expression, been shown to be critically involved in VEGFR3/VEGFC signaling, resulting in reduced lymphangiogenic sprouting. In addition, Notch1-Dll4 blockade leads to compromised expression of distinct lymphatic markers and to dilation of collecting lymphatic vessels with reduced and disorganized mural cell coverage. Finally, Dll4-blockade impairs wound closure and severely affects lymphangiogenesis during the wound healing in adult mouse skin. Thus, our study demonstrates for the first time in a mammalian system that Notch1-Dll4 signaling pathway regulates postnatal lymphatic development and pathologic lymphangiogenesis.


AIDS ◽  
2010 ◽  
Vol 24 (14) ◽  
pp. 2161-2170 ◽  
Author(s):  
Madhulika Sharma ◽  
Shannon Callen ◽  
Da Zhang ◽  
Pravin C Singhal ◽  
Gregory B Vanden Heuvel ◽  
...  

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