scholarly journals Cylindromatosis (CYLD), a Deubiquitinase, Attenuates Inflammatory Signaling Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells

2017 ◽  
Vol 42 (5) ◽  
pp. 942-950 ◽  
Author(s):  
Tadaatsu Imaizumi ◽  
Ryo Hayakari ◽  
Shojiro Watanabe ◽  
Tomomi Aizawa ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mesangial Cells ◽  
Toll Like Receptor ◽  
Inflammatory Signaling ◽  
Human Mesangial Cells

Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells

2014 ◽  
Vol 19 (5) ◽  
pp. 761-770 ◽  
Author(s):  
Tadaatsu Imaizumi ◽  
Tomomi Aizawa ◽  
Chihiro Segawa ◽  
Michiko Shimada ◽  
Kazushi Tsuruga ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Toll Like Receptor ◽  
Human Mesangial Cells

Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 844-854 ◽  
Author(s):  
Quan Zhuang ◽  
Jiarui Ou ◽  
Sheng Zhang ◽  
Yingzi Ming
Keyword(s):  
Signaling Pathways ◽  
Tissue Injury ◽  
Signaling Networks ◽  
Toll Like Receptor ◽  
Inflammatory Signaling ◽  
Inflammatory Cascade ◽  
Inflammatory Processes ◽  
Membrane Bound ◽  
G Protein Coupled ◽  
Receptor Cx3cr1

During inflammation, chemokines play a central role by mediating the activation of inflammatory cascade responses in tissue injury. Among more than 200 chemokines, CX3CL1 is a special chemotactic factor existing in both membrane-bound and soluble forms. Its only receptor, CX3CR1, is a member of the G protein-coupled receptor superfamily. The CX3CL1/CX3CR1 axis can affect many inflammatory processes by communicating with different inflammatory signaling pathways, such as JAK-STAT, Toll-like receptor, MAPK, AKT, NF-κB, Wnt/β-catenin, as well as others. These inflammatory networks are involved in much pathology. Determining the crosstalk between the CX3CL1/CX3CR1 axis and these inflammatory signaling pathways could contribute to solving problems in tissue injury, and the CX3CL1/CX3CR1 axis may be a better therapeutic target than inflammatory signaling pathways for preventing tissue injury due to the complexity of inflammatory signaling networks.

scholarly journals Inflammatory Chemokine Expression via Toll-Like Receptor 3 Signaling in Normal Human Mesangial Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hiroshi Tanaka ◽  
Tadaatsu Imaizumi
Keyword(s):  
Renal Disease ◽  
Signaling Pathways ◽  
Viral Infections ◽  
Mesangial Cells ◽  
Experimental Studies ◽  
Renal Diseases ◽  
Glomerular Diseases ◽  
Human Mesangial Cells ◽  
Normal Human ◽  
Few Data

The innate and adaptive immune systems have been reported to play an important role in the pathogenesis of glomerular diseases. Since viral infections may trigger the development of inflammatory renal disease or the worsening of preexisting renal disease, recent studies have focused on the involvement of toll-like receptors (TLRs) and their signaling pathways in the inflammatory processes of glomerular cells. Viral double-stranded RNA (dsRNA) can activate not only TLR3 located within intracellular endosomes but also retinoic-acid-inducible-gene-I- (RIG-I-) like helicase receptors located within the cytosol. RIG-I and melanoma differentiation-associated gene 5 (MDA5) are members of the RNA helicase family in the cytosol, and both act as pathogen recognition receptors. The activation of TLRs and their downstream immune responses can be induced by both infectious pathogens and noninfectious stimuli such as endogenous ligands, and this mechanism may be involved in the pathogenesis of autoimmune renal diseases. However, there are few data on the interaction between TLR3, MDA5, and RIG-I in autoimmune glomerular diseases. Based on our recent experimental studies using cultured normal human mesangial cells (MCs), we found that novel TLR3-mediated signaling pathways in MCs may be involved in the pathogenesis of glomerular diseases. In the present paper, we summarize our recent findings.

Interaction between Interferon-Stimulated Gene 56 and Melanoma Differentiation-Associated Gene 5 in Toll-Like Receptor 3 Signaling in Normal Human Mesangial Cells

2013 ◽  
Vol 37 (2) ◽  
pp. 118-125 ◽  
Author(s):  
Tadaatsu Imaizumi ◽  
Tomomi Aizawa-Yashiro ◽  
Tomoh Matsumiya ◽  
Hidemi Yoshida ◽  
Shojiro Watanabe ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Toll Like Receptor ◽  
Human Mesangial Cells ◽  
Normal Human

scholarly journals Activated Coagulation Factor X: A Novel Mitogenic Stimulus for Human Mesangial Cells

2001 ◽  
Vol 12 (5) ◽  
pp. 891-899 ◽  
Author(s):  
RAFFAELLA MONNO ◽  
GIUSEPPE GRANDALIANO ◽  
ROBERTA FACCIO ◽  
ELENA RANIERI ◽  
CARMELA MARTINO ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dna Synthesis ◽  
Signaling Pathways ◽  
Phospholipase C ◽  
Serine Protease ◽  
Mesangial Cells ◽  
Factor X ◽  
Mitogenic Effect ◽  
Human Mesangial Cells

Abstract. Intraglomerular activation of the coagulation cascade is a common feature of mesangioproliferative glomerulonephritis. Besides thrombin, very little is known about the cellular effects of other components of the coagulation system. This study investigated the effect of activated factor X (FXa) on cultured human mesangial cells. This serine protease induced a significant and dose-dependent increase in DNA synthesis. In addition to its mitogenic effect, FXa caused a striking upregulation of platelet-derived growth factor (PDGF) A and B chain gene expression. Next, the intracellular mitogenic signaling pathways activated by FXa were investigated. FXa induced a rapid spike in cytosolic calcium concentration followed by a sustained plateau. This response was not influenced by the downregulation of thrombin receptors. In addition, FXa stimulated a significant upregulation of different tyrosine-phosphorylated proteins. One of these phosphorylated cellular proteins was represented by the c-jun N-terminal kinase, a member of the mitogen-activated protein kinase family. To evaluate the role of FXa enzymatic activity and of PDGF autocrine secretion, FXa-induced DNA synthesis was studied in the presence of leupeptin, a specific serine protease inhibitor, and neutralizing anti-PDGF antibody. To investigate the role of tyrosine kinase (TK) activation on FXa mitogenic effect, FXa-stimulated thymidine uptake was evaluated in the presence of genistein and herbimycin A, two powerful and specific TK inhibitors. FXa-elicited DNA synthesis was also examined after protein kinase C (PKC) downregulation by prolonged incubation with phorbol-12-myristate-13-acetate to study the influence of the phospholipase C-PKC axis. The proliferative effect of FXa required its proteolytic activity, and the activation of TK was only partially dependent on PKC activation while it was PDGF independent. Finally, it was shown by reverse transcription-PCR that mesangial cells do not express the signaling splicing variant of the putative FXa receptor, effector protease receptor-1. In conclusion, the present study demonstrated that FXa is a powerful mitogenic factor for human mesangial cells, and it induces its cellular effect not through effector protease receptor-1, but most likely by binding a protease-activated receptor and activating phospholipase C—PKC and TK signaling pathways.

Sign in / Sign up

Export Citation Format

Share Document