scholarly journals Tetraspanins Regulate ADAM10-Mediated Cleavage of TNF-α and Epidermal Growth Factor

2008 ◽  
Vol 181 (10) ◽  
pp. 7002-7013 ◽  
Author(s):  
Cécile Arduise ◽  
Toufik Abache ◽  
Lei Li ◽  
Martine Billard ◽  
Aurélie Chabanon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tnf Α ◽  
Epidermal Growth

scholarly journals Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2437-2453
Author(s):  
Pauline E Schneeberger ◽  
Fanny Kortüm ◽  
Georg Christoph Korenke ◽  
Malik Alawi ◽  
René Santer ◽  
...  
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Developmental Delay ◽  
Autonomic Nervous ◽  
Organ Systems ◽  
Tnf Α ◽  
Epidermal Growth ◽  
The Impact

Abstract In pleiotropic diseases, multiple organ systems are affected causing a variety of clinical manifestations. Here, we report a pleiotropic disorder with a unique constellation of neurological, endocrine, exocrine, and haematological findings that is caused by biallelic MADD variants. MADD, the mitogen-activated protein kinase (MAPK) activating death domain protein, regulates various cellular functions, such as vesicle trafficking, activity of the Rab3 and Rab27 small GTPases, tumour necrosis factor-α (TNF-α)-induced signalling and prevention of cell death. Through national collaboration and GeneMatcher, we collected 23 patients with 21 different pathogenic MADD variants identified by next-generation sequencing. We clinically evaluated the series of patients and categorized the phenotypes in two groups. Group 1 consists of 14 patients with severe developmental delay, endo- and exocrine dysfunction, impairment of the sensory and autonomic nervous system, and haematological anomalies. The clinical course during the first years of life can be potentially fatal. The nine patients in Group 2 have a predominant neurological phenotype comprising mild-to-severe developmental delay, hypotonia, speech impairment, and seizures. Analysis of mRNA revealed multiple aberrant MADD transcripts in two patient-derived fibroblast cell lines. Relative quantification of MADD mRNA and protein in fibroblasts of five affected individuals showed a drastic reduction or loss of MADD. We conducted functional tests to determine the impact of the variants on different pathways. Treatment of patient-derived fibroblasts with TNF-α resulted in reduced phosphorylation of the extracellular signal-regulated kinases 1 and 2, enhanced activation of the pro-apoptotic enzymes caspase-3 and -7 and increased apoptosis compared to control cells. We analysed internalization of epidermal growth factor in patient cells and identified a defect in endocytosis of epidermal growth factor. We conclude that MADD deficiency underlies multiple cellular defects that can be attributed to alterations of TNF-α-dependent signalling pathways and defects in vesicular trafficking. Our data highlight the multifaceted role of MADD as a signalling molecule in different organs and reveal its physiological role in regulating the function of the sensory and autonomic nervous system and endo- and exocrine glands.

Epidermal growth factor enhances TNF-α-induced priming of human neutrophils

2005 ◽  
Vol 96 (2) ◽  
pp. 203-210 ◽  
Author(s):  
Przemysław Lewkowicz ◽  
Henryk Tchórzewski ◽  
Katarzyna Dytnerska ◽  
Małgorzata Banasik ◽  
Natalia Lewkowicz
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Neutrophils ◽  
Tnf Α ◽  
Epidermal Growth

scholarly journals Epidermal growth factor/TNF-α transactivation modulates epithelial cell proliferation and apoptosis in a mouse model of parenteral nutrition

2012 ◽  
Vol 302 (2) ◽  
pp. G236-G249 ◽  
Author(s):  
Yongjia Feng ◽  
Daniel H. Teitelbaum
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Mouse Model ◽  
Parenteral Nutrition ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Epidermal Growth ◽  
Factor Α ◽  
Egf Signaling

Epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) signaling are critical for effective proliferative and apoptotic actions; however, little is known about the codependency of these signaling pathways in the intestinal epithelium. Because total parenteral nutrition (TPN) is associated with loss of intestinal epithelial cell (IEC) proliferation and increased apoptosis, we utilized a mouse model to explore these transactivation pathways in small bowel epithelium. Mice underwent intravenous cannulation and were given enteral nutrition or TPN for 7 days. Outcomes included IEC proliferation, apoptosis, and survival. To address transactivation or dependence of EGF and TNF on IEC physiology, TNF-α receptor knockout (KO) mice, TNFR1-KO, R2-KO, or R1R2-double KO, were used. Exogenous EGF and pharmacological blockade of ErbB1 were performed in other groups to examine the relevance of the ErB1 pathway. TPN increased IEC TNFR1 and decreased EGF and ErbB1 abundance. Loss of IEC proliferation was prevented by exogenous EGF or blockade of TNFR1. However, EGF action was prevented without effective TNFR2 signaling. Also, blockade of TNFR1 could not prevent loss of IEC proliferation without effective ErbB1 signaling. TPN increased IEC apoptosis and was due to increased TNFR1 signaling. Exogenous EGF or blockade of TNFR1 could prevent increased apoptosis, and both pathways were dependent on effective ErbB1 signaling. Exogenous EGF prevented increased apoptosis in mice lacking TNFR2 signaling. TPN mice had significantly decreased survival vs. controls, and this was associated with the TNFR1 signaling pathway. We concluded that these findings identify critical mechanisms that contribute to TPN-associated mucosal atrophy via altered TNF-α/EGF signaling. It emphasizes the importance of both TNFR1 and TNFR2 pathways, as well as the strong interdependence on an intact EGF/ErbB1 pathway.

scholarly journals Rapid and transient induction of cyclo-oxygenase 2 by epidermal growth factor in human amnion-derived WISH cells

1997 ◽  
Vol 321 (3) ◽  
pp. 677-681 ◽  
Author(s):  
Douglas J. PERKINS ◽  
Douglas A. KNISS
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Protein Expression ◽  
De Novo ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Epidermal Growth ◽  
Cox 2 ◽  
Dose Dependent ◽  
Cox 1

The central enzyme in the prostaglandin (PG) biosynthetic cascade is PGH2 synthase or cyclo-oxygenase (COX). At present, two distinct isoforms of PGH2 synthase/COX have been identified: COX-1 and COX-2. In many systems, COX-1 is a constitutively expressed isoform that is responsible for normal physiological production of PGs, whereas COX-2 is an inducible isoform that responds to cytokines, endotoxin and growth factors by producing high levels of PGs. The regulation of COX-2 mRNA and protein, and the subsequent production of PGE2, were therefore examined in amnion-derived WISH cells stimulated with epidermal growth factor (EGF). Treatment of WISH cells with EGF (0.01Ő100 ng/ml) elicited dose-dependent synthesis of COX-2 mRNA and protein de novo. In addition, stimulation of WISH cells with EGF (10 ng/ml) induced steady-state levels of COX-2 mRNA and protein that appeared within 30 min and then declined rapidly to near baseline levels within 2Ő4 h. In contrast, COX-1 protein was unchanged in response to treatment with EGF. PGE2 production was also rapid and transient. Preincubation of cells with the novel COX-2 enzymic inhibitor NS-398 (10-5Ő10-10 M) completely prevented PGE2 formation in a dose-dependent manner. Preincubation of cells in dexamethasone (Dex; 0.1 ƁM), however, resulted in only a 31% decrease in PGE2 formation in response to EGF (10 ng/ml) while completely attenuating PGE2 biosynthesis in tumour necrosis factor α (TNF-α)-stimulated cells. In addition, Dex (0.1 ƁM) was only partly effective at preventing EGF-induced COX-2 mRNA and protein expression de novo, whereas Dex completely inhibited TNF-α-promoted COX-2 mRNA and protein expression. Thus the results presented here demonstrate that EGF induces the rapid but transient expression of COX-2 mRNA and protein and the subsequent production of PGE2 in WISH cells.

scholarly journals Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

2016 ◽  
Vol 24 (3) ◽  
pp. 307-317
Author(s):  
Melike Erol-Demirbilek ◽  
Nedret Kilic ◽  
Hatice Ferhan Komurcu
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Epidermal Growth Factor ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Thioredoxin System ◽  
Epidermal Growth ◽  
Cerebral Ischemic ◽  
Necrosis Factor

Abstract Background: Thioredoxin reductase (TrxR), epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains. Methods: Sprague-Dawley rats divided into three groups. Rats in control group were not subjected to any of treatments and their brains were removed under anesthesia. Middle cerebral arters were exposed but not occluded for the sham-operated rats. Animals were subjected to permanent middle cerebral arter occlusion (MCAO) in MCAO-operated group. The rats were decapitated at 16 hours (h), 48 h and 96 h after sham operation and focal cerebral ischemia. TrxR activities, EGF and TNF-α levels were measured in ischemic and non-ischemic hemispheres for all groups. Results: In group MCAO, TrxR activities were significantly low at 48 h in ischemic hemisphere in comparison to control. After the 48 h, a remarkable increase was observed at 96 h. EGF and TNF-α levels were substantially high at 96 h in group MCAO of ischemic brain. Conclusion: TrxR activity was reduced by oxidative stress which was formed by ischemia. EGF levels increased to exhibit neurotrophic and neuroprotective effects. After ischemia, TNF-α levels increased as a response to the tissue damage. Further studies with a higher number of experimental subjects and shorter or longer periods such as from first 30 minutes up to 3 months may be more informative to show the time-dependent variations in TrxR, EGF and TNF-α in cerebral ischemic injury.

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