EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by α2A-adrenoreceptor in intestinal epithelial cells: A role in wound healing

2007 ◽  
Vol 574 (2-3) ◽  
pp. 85-93 ◽  
Author(s):  
Bénédicte Buffin-Meyer ◽  
Pierre-Antoine Crassous ◽  
Christine Delage ◽  
Colette Denis ◽  
Stéphane Schaak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Egf Receptor ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Receptor Transactivation ◽  
Stimulation Of

Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals

2007 ◽  
Vol 292 (1) ◽  
pp. G39-G52 ◽  
Author(s):  
Masahiro Iizuka ◽  
Kenji Sasaki ◽  
Yohei Hirai ◽  
Kenichi Shindo ◽  
Shiho Konno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Epithelial Cells ◽  
Egf Receptor ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial cells. Our preliminary study suggested a novel function of epimorphin in enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads to cell injury and death and is suggested to be a key contributor to pathogenesis of inflammatory bowel disease. This study was conducted to determine whether epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell line IEC-6 was cultured with epimorphin (10 and 20 μg/ml), and the life span of IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold ( P < 0.0006) by treatment with epimorphin. We then examined the epimorphin signaling pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor, activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways, phosphorylated Bad, and induced Bcl-XL and survivin. Hydrogen peroxide (1 mM) induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished (88.7%) cell death induced by hydrogen peroxide ( P < 0.0001). This protective effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3 kinase ( P < 0.0001) or EGF receptor-neutralizing antibody ( P = 0.0007). In wound assays, the number of migrated cells in the wound area decreased (72.5%) by treatment with 30 μM hydrogen peroxide, but epimorphin increased the number of migrated cells 3.18-fold ( P < 0.0001). These results support a novel function of epimorphin in protecting IEC from oxidative stress. This anti-oxidative function of epimorphin is dramatic and is likely mediated by the activation of EGF receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt signaling pathways and through the induction of anti-apoptotic factors.

Epidermal growth factor and interleukin-1β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells

2004 ◽  
Vol 287 (6) ◽  
pp. G1188-G1193 ◽  
Author(s):  
Katsuhiko Kitagawa ◽  
Yoshinori Hamada ◽  
Yasunori Kato ◽  
Koji Nakai ◽  
Mikio Nishizawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Simultaneous Addition ◽  
Epidermal Growth ◽  
Inos Induction

Epidermal growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1β in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-κB (IκB), NF-κB, and Akt, were analyzed. IL-1β stimulated the degradation of IκB and the activation of NF-κB but had no effect on iNOS induction. EGF, which had no effect on the NF-κB activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1β stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1β stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-κB through IκB kinase, respectively. Simultaneous addition of EGF and IL-1β can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury.

Monochloramine induces reorganization of nuclear speckles and phosphorylation of SRp30 in human colonic epithelial cells: role of protein kinase C

2003 ◽  
Vol 285 (5) ◽  
pp. C1294-C1303 ◽  
Author(s):  
Ya-Qin Zhu ◽  
Yu Lu ◽  
Xiao-Di Tan
Keyword(s):  
Gastrointestinal Tract ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Morphological Changes ◽  
Sr Proteins ◽  
Mrna Splicing ◽  
Intestinal Epithelial ◽  
Nuclear Speckles ◽  
Colonic Epithelial Cells ◽  
Stimulation Of

Intestinal epithelial cells are constantly stimulated by reactive oxidant metabolites (ROMs) in inflamed mucosa. Monochloramine (NH2Cl), a cell-permeant ROM, is particularly relevant to the pathogenesis of inflammation in the gastrointestinal tract. Nuclear speckles, a unique nuclear subcompartment, accumulate a family of proteins, namely, serine- and arginine-rich (SR) proteins. They play important roles in regulation of pre-mRNA splicing. Currently, little is known about the link between inflammatory stimulation and the pre-mRNA splicing process, although gene expression is changed in inflamed tissues. The present study was designed to investigate whether stimulation of human colonic epithelial cells (HT-29 and Caco-2 cell lines) with NH2Cl affects nuclear speckles and their components. By indirect immunofluorescence, nuclear speckles have been shown to undergo rapid aggregation after NH2Cl stimulation. By utilizing Western blotting, SRp30 (a subset of SR proteins) in intestinal epithelial cells was found to be phosphorylated after NH2Cl treatment, whereas other SR proteins were not responsive to NH2Cl stimulation. The cytotoxic effect of NH2Cl was excluded by both negative lactate dehydrogenase assay and propidium iodide staining. Therefore, NH2Cl-induced morphological changes on nuclear speckles and phosphorylated SRp30 do not result from intestinal epithelial injury. Furthermore, the effect of NH2Cl on nuclear speckles and SRp30 was blocked by bisindolylmaleimide I, a selective PKC inhibitor. Together, the available data suggest that stimulation of intestinal epithelial cells with NH2Cl results in a consequent change on pre-mRNA splicing machinery via a distinctive signal pathway involving activation of PKC. This effect may contribute to oxidant-induced pathophysiological changes in the gastrointestinal tract.

Tu1865 IL-28 Signaling in Intestinal Epithelial Cells Leads to a Revised Mucosal Wound Healing

2012 ◽  
Vol 142 (5) ◽  
pp. S-864
Author(s):  
Heike Dornhoff ◽  
Konstantin Fietkau ◽  
Sean Doyle ◽  
Markus F. Neurath ◽  
Jürgen Siebler
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Mucosal Wound

W1600 STAT3 Links IL-22 Signalling in Intestinal Epithelial Cells to Mucosal Wound Healing

2009 ◽  
Vol 136 (5) ◽  
pp. A-700
Author(s):  
Geethanjali Pickert ◽  
Clemens Neufert ◽  
Moritz Leppkes ◽  
Alexei Nikolaev ◽  
Hans-Anton Lehr ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Mucosal Wound

scholarly journals STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing

2009 ◽  
Vol 206 (7) ◽  
pp. 1465-1472 ◽  
Author(s):  
Geethanjali Pickert ◽  
Clemens Neufert ◽  
Moritz Leppkes ◽  
Yan Zheng ◽  
Nadine Wittkopf ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Genetically Engineered ◽  
Conditional Knockout ◽  
Cellular Stress Response ◽  
Cytokine Signaling ◽  
Intestinal Epithelial ◽  
Genetically Engineered Mice ◽  
Mucosal Wound

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing.

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