scholarly journals Lactobacillus casei extracellular vesicles stimulate EGFR pathway likely due to the presence of proteins P40 and P75 bound to their surface

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christine Bäuerl ◽  
José M. Coll-Marqués ◽  
Carmen Tarazona-González ◽  
Gaspar Pérez-Martínez
Keyword(s):  
Extracellular Vesicles ◽  
Lactobacillus Casei ◽  
Culture Supernatant ◽  
External Surface ◽  
Growth Factor Receptor ◽  
Lipoteichoic Acid ◽  
Proteinase K ◽  
Protective Effects ◽  
Epidermal Growth ◽  
20 Nm

Abstract In the complex interplay of beneficial bacteria with the host, there are few examples of bacterial metabolites and effector molecules that have been consistently identified. Protective effects on the intestinal epithelium have been ascribed to P40 and P75, two well characterized cell wall muramidases, present in the culture supernatant of strains belonging to the taxon Lactobacillus casei/paracasei/rhamnosus. This work reports that Lactobacillus casei BL23 extracellular vesicles (BL23 EVs) have a small size (17–20 nm or 24–32 nm, depending on the method used) and contain lipoteichoic acid (LTA). Interestingly, all detected P40 and most of P75 were associated to EVs and possibly located at their external surface, as shown by proteinase K digestion. Biosensor assays showed that both proteins bind LTA and vesicles, suggesting that they could bind to ligands like LTA present on BL23 EVs. Native BL23 EVs have a moderate proinflammatory effect and they were able to induce phosphorylation of the epidermal growth factor receptor (EGFR), showing an effect similar to purified P40 and P75 and leading to the conclusion that the activity described in the supernatant (postbiotic) of these bacteria would be mainly due to P40 and P75 bound to EVs.

scholarly journals Senescent cholangiocytes release extracellular vesicles that alter target cell phenotype via the epidermal growth factor receptor

2020 ◽  
Vol 40 (10) ◽  
pp. 2455-2468 ◽  
Author(s):  
Mohammed S. Al Suraih ◽  
Christy E. Trussoni ◽  
Patrick L. Splinter ◽  
Nicholas F. LaRusso ◽  
Steven P. O’Hara
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Extracellular Vesicles ◽  
Target Cell ◽  
Growth Factor Receptor ◽  
Cell Phenotype ◽  
Epidermal Growth

scholarly journals Suppression of Amphiregulin/Epidermal Growth Factor Receptor Signals Contributes to the Protective Effects of Quercetin in Cirrhotic Rats

2011 ◽  
Vol 141 (7) ◽  
pp. 1299-1305 ◽  
Author(s):  
María J. Cuevas ◽  
Juliana Tieppo ◽  
Norma Possa Marroni ◽  
María J. Tuñón ◽  
Javier González-Gallego
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Protective Effects ◽  
Epidermal Growth

scholarly journals Sensory neurons sprouting is dependent on osteoclast-derived extracellular vesicles involving the activation of epidermal growth factor receptors

2018 ◽  
Author(s):  
Estrela Neto ◽  
Luís Leitão ◽  
José Mateus ◽  
Daniela M. Sousa ◽  
Francisco Conceição ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Extracellular Vesicles ◽  
Sensory Neurons ◽  
Growth Factor Receptor ◽  
Signal Propagation ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Peripheral Innervation ◽  
Epidermal Growth

AbstractThe patterning of peripheral innervation is accomplished through the tissue expression, in specific space and timeframe, of attractive or repulsive axonal guidance cues. At the bone microenvironment, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor, netrin-1 and others were described to regulate the nerve ingrowth towards the bone compartment, by acting directly on receptors expressed at the nerve terminals. Interestingly, besides the gradient of soluble factors, neurons were described to be responsive to extracellular vesicles (EV) derived from myelinating cells and mesenchymal stem cells.Here we provide evidence on a new mechanism by which peripheral innervation can be coordinated. We show that sensory nerves outgrowth and electric signal propagation are dependent on the EV secreted by osteoclasts, the bone resorbing cells. Furthermore, we demonstrate that the axonal sprouting is achieved through the activation of epidermal-growth factor receptor (EGFR) family signaling pathway. We proved that the EV-depleted osteoclast secretome leads to a significant decrease of neurons firing rate and axonal sprouting, concomitant with a decrease of EGFR/ErbB2 activation levels. Excitingly, the proteomic analysis of the osteoclast-derived EV cargo shows a high correlation with synaptic components reinforcing the role on sensory neurons/osteoclast crosstalk.Our findings that osteoclast-derived EV hold effect in axonal outgrowth, contributing actively to the dynamics of the sensory neurons sprouting and electrophysiology, is a step toward unraveling target mechanisms to control electrical signal propagation and nerve fibers sprouting and consequently open new avenues for the development of innovative therapies to control bone pain.Significance StatementSensory nerve fibers sprouting in bone pathologies is highly associated with pain. Thus, understanding the mechanisms behind sensory nerves ingrowth, sprouting and electrical activity, within the bone compartment, is essential for improving the strategies to overcome pain in bone disorders. We provide a new mechanism on the sensory nerves sprouting, indicating that the effect is dependent on the extracellular vesicles (EV) released by osteoclasts, through the epidermal growth factor receptor family targeting, by integrin independent pathways. We show different electrophysiology patterns being triggered in the presence of osteoclasts secretome and the abolishment of sensory neurons firing rate in EV-depleted conditions. Overall, our results elucidate novel mechanisms on the peripheral nerves sprouting, essential for pursuing new targets for bone pain therapies.

scholarly journals Antagonistic regulation of swelling-activated Cl− current in rabbit ventricle by Src and EGFR protein tyrosine kinases

2005 ◽  
Vol 288 (6) ◽  
pp. H2628-H2636 ◽  
Author(s):  
Zuojun Ren ◽  
Clive M. Baumgarten
Keyword(s):  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Tyrosine Phosphatase ◽  
Growth Factor Receptor ◽  
Equilibrium Potential ◽  
Protein Tyrosine ◽  
Epidermal Growth ◽  
20 Nm ◽  
Multiple Signaling ◽  
Egfr Kinase

Regulation of swelling-activated Cl− current ( ICl,swell) is complex, and multiple signaling cascades are implicated. To determine whether protein tyrosine kinase (PTK) modulates ICl,swell and to identify the PTK involved, we studied the effects of a broad-spectrum PTK inhibitor (genistein), selective inhibitors of Src (PP2, a pyrazolopyrimidine) and epidermal growth factor receptor (EGFR) kinase (PD-153035), and a protein tyrosine phosphatase (PTP) inhibitor (orthovanadate). ICl,swell evoked by hyposmotic swelling was increased 181 ± 17% by 100 μM genistein, and the genistein-induced current was blocked by the selective ICl,swell blocker tamoxifen (10 μM). Block of Src with PP2 (10 μM) stimulated tamoxifen-sensitive ICl,swell by 234 ± 27%, mimicking genistein, whereas the inactive analog of PP2, PP3 (10 μM), had no effect. Moreover, block of PTP by orthovanadate (1 mM) inhibited ICl,swell and prevented its stimulation by PP2. In contrast with block of Src, block of EGFR kinase with PD-153035 (20 nM) inhibited ICl,swell. Several lines of evidence argue that the PP2-stimulated current was ICl,swell: 1) the stimulation was volume dependent, 2) the current was blocked by tamoxifen, 3) the current outwardly rectified with both symmetrical and physiological Cl− gradients, and 4) the current reversed near the Cl− equilibrium potential. To rule out contributions of other currents, Cd2+ (0.2 mM) and Ba2+ (1 mM) were added to the bath. Surprisingly, Cd2+ suppressed the decay of ICl,swell, and Cd2+ plus Ba2+ eliminated time-dependent currents between −100 and +100 mV. Nevertheless, these divalent ions did not eliminate ICl,swell or prevent its stimulation by PP2. The results indicate that tyrosine phosphorylation controls ICl,swell, and regulation of ICl,swell by the Src and EGFR kinase families of PTK is antagonistic.

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