Hes-1-targeting siRNA inhibits the maturation of murine myeloid-derived dendritic cells

2013 ◽  
Vol 8 (11) ◽  
pp. 1102-1111
Author(s):  
Guoliang Chen ◽  
Chunyan Yu ◽  
Feiyue Xing ◽  
Pengtao You ◽  
Jingfang Di ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Notch Signaling Pathway ◽  
Murine Bone Marrow ◽  
Mhc Ii ◽  
Pathway Activation

AbstractActivation of Notch by Jagged-1 may plays a pivotal role in maturation of dendritic cells (DCs), but the mechanism has not been completely defined. In the present study, Hes-1 (Hairy/enhancer-of-split)-targeting siRNA was used to confirm a role of Jagged-1-Notch signaling pathway activation in maturation of murine bone marrow-derived DCs and to search for a target that plays a critical role. The results showed that compared with the control, lipopolysaccharide or Zymosan A groups, Jagged-1 (a soluble Jagged 1/Fc chimera protein) effectively increased expression of Hes-1 and Deltex-1 mRNA, which could be reversed by DAPT (2, 4-diamino-5-phenylthiazole), a specific inhibitor of the Notch signaling pathway. Hes-1-targeting siRNA could successfully down-regulate the endogenous Hes-1 expression in the DCs. Concurrently, a significant down-regulation of CD40, CD80, CD86 and MHC-II expressions on the surface of the DCs was found with the reduction of IL-12 yielded by the DCs. Our results demonstrate that Hes-1-targeting siRNA can inhibit the maturation of the DCs induced by Jagged-1, indicating Hes-1 may be an important target of Notch signaling mediating the maturation of DCs.

scholarly journals ProteinO-Fucosyltransferase 1 Expression Impacts Myogenic C2C12 Cell Commitment via the Notch Signaling Pathway

2014 ◽  
Vol 35 (2) ◽  
pp. 391-405 ◽  
Author(s):  
Audrey Der Vartanian ◽  
Aymeric Audfray ◽  
Bilal Al Jaam ◽  
Mathilde Janot ◽  
Sébastien Legardinier ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Critical Role ◽  
C2c12 Cell ◽  
Notch Signaling Pathway ◽  
Skeletal Muscle Regeneration ◽  
Pathway Activation ◽  
Activated State ◽  
Cell Commitment

The Notch signaling pathway plays a crucial role in skeletal muscle regeneration in mammals by controlling the transition of satellite cells from quiescence to an activated state, their proliferation, and their commitment toward myotubes or self-renewal. O-fucosylation on Notch receptor epidermal growth factor (EGF)-like repeats is catalyzed by the proteinO-fucosyltransferase 1 (Pofut1) and primarily controls Notch interaction with its ligands. To approach the role of O-fucosylation in myogenesis, we analyzed a murine myoblastic C2C12 cell line downregulated forPofut1expression by short hairpin RNA (shRNA) inhibition during the time course of differentiation. Knockdown ofPofut1affected the signaling pathway activation by a reduction of the amount of cleaved Notch intracellular domain and a decrease in downstream Notch target gene expression. Depletion in Pax7+/MyoD−cells and earlier myogenic program entrance were observed, leading to an increase in myotube quantity with a small number of nuclei, reflecting fusion defects. The rescue ofPofut1expression in knockdown cells restored Notch signaling activation and a normal course in C2C12 differentiation. Our results establish the critical role of Pofut1 on Notch pathway activation during myogenic differentiation.

scholarly journals Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1264-1273 ◽  
Author(s):  
Melanie G. Cornejo ◽  
Vinciane Mabialah ◽  
Stephen M. Sykes ◽  
Tulasi Khandan ◽  
Cristina Lo Celso ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Differentiation ◽  
Notch Signaling Pathway ◽  
Developmental Pathways ◽  
Lineage Specification ◽  
Hematopoietic Stem

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.

scholarly journals Epidermoid cyst in a patient with Alagille syndrome: Coincidence or connection?

2020 ◽  
Vol 11 ◽  
pp. 432
Author(s):  
Akhil Surapaneni ◽  
John Kuo ◽  
Min Wang ◽  
Ramsey Ashour
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Epidermoid Cyst ◽  
Alagille Syndrome ◽  
Notch Signaling Pathway ◽  
Syndrome Patient ◽  
Benign Lesions ◽  
Genetic Syndrome ◽  
Epidermoid Cysts

Background: Alagille syndrome is a rare genetic syndrome, which arises due to defects in the Notch signaling pathway, resulting in liver, cardiopulmonary, renal, skeletal, and ophthalmologic problems, among others. Epidermoid cysts are rare congenital benign lesions that develop from ectopic ectodermal cell rests formed during neurulation. Case Description: A 24-year-old Alagille syndrome patient presented with hearing loss and was found to have a sizable posterior fossa mass. He underwent craniotomy for uneventful resection of the lesion, which was found to be an epidermoid cyst. Conclusion: While our case may represent a coincidental occurrence of two pathologies presenting together, given that epidermoid cysts arise from aberrant neurulation, and in light of the crucial role of the Notch signaling pathway both in normal neurogenesis and in the pathogenesis of Alagille syndrome, we hypothesize a possible association between these entities.

scholarly journals The Carcinogenic Role of the Notch Signaling Pathway in the Development of Hepatocellular Carcinoma

2019 ◽  
Vol 10 (6) ◽  
pp. 1570-1579 ◽  
Author(s):  
Qinfeng Huang ◽  
Junhong Li ◽  
Jinghui Zheng ◽  
Ailing Wei
Keyword(s):  
Hepatocellular Carcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

scholarly journals A role of the LIN-12/Notch signaling pathway in diversifying the non-striated egg-laying muscles in C. elegans

2014 ◽  
Vol 389 (2) ◽  
pp. 137-148 ◽  
Author(s):  
Jared J. Hale ◽  
Nirav M. Amin ◽  
Carolyn George ◽  
Zachary Via ◽  
Herong Shi ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Egg Laying ◽  
C Elegans

Association between Notch signaling pathway and cancer

2013 ◽  
Vol 19 (4) ◽  
pp. 427-437
Author(s):  
Nadežda Lachej ◽  
Janina Didžiapetrienė ◽  
Birutė Kazbarienė ◽  
Daiva Kanopienė ◽  
Violeta Jonušienė
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Treatment Method ◽  
Notch Signaling Pathway ◽  
Published Data ◽  
Undifferentiated Cells ◽  
Oncologic Diseases ◽  
Worse Prognosis

Background. The components of the Notch signaling pathway are important in maintaining the balance involved in cell proliferation, apoptosis and differentiation. Therefore, dysfunction of the Notch prevents differentiation, ultimately guiding undifferentiated cells toward malignant transformation. The aim of this article is to present recently published data concerning the role of the Notch signaling pathway components in development and prognosis of oncologic diseases, in occurrence of resistance to cytostatic agents and importance in creating of new cancer treatment approaches. Materials and methods. The Pubmed was the main source of looking for information for this article. Results. Recent investigations show that disorders of the Notch signaling pathway are associated with development of some human haematological and solid cancers. In different tissues and organs this active pathway can act as a tumor suppressor or an oncogene. Accordingly, the increased or decreased expression of its components is defined. Most of published data show that the increased expression of Notch pathway components correlates with a worse prognosis of cancer and a shorter survival. Recently, the Notch pathway has been reported to be involved in drug resistance. The modulation of the Notch signaling pathway could be helpful in treatment of some tumors with abnormal activity of this pathway’s components. Therefore changes in the expression of Notch components could become important predictive factors, helpful in selecting the proper treatment method. Conclusions. The results of recent studies are very important, since the detecting of the prognostic and predictive value of components of the Notch signaling pathway can allow creating new and improving already known methods of cancer diagnostic and treatment.

Role of Hairless and Suppressor of Hairless in the Notch signaling pathway in Drosophila

1995 ◽  
Vol 84 (1-2) ◽  
pp. 89-89
Author(s):  
M. Lecourtois ◽  
C. Brou ◽  
F. Logeat ◽  
A. Israel ◽  
F. Schweisguth
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Suppressor Of Hairless
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