scholarly journals Probiotic-Derived Polyphosphate Accelerates Intestinal Epithelia Wound Healing through Inducing Platelet-Derived Mediators

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shotaro Isozaki ◽  
Hiroaki Konishi ◽  
Mikihiro Fujiya ◽  
Hiroki Tanaka ◽  
Yuki Murakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Intestinal Inflammation ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Intestinal Barrier Function ◽  
Ki 67

Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), is an intractable intestinal inflammation associated with the disruption of the intestinal mucosa. We previously demonstrated that Lactobacillus brevis-derived long-chain polyphosphate (poly P) improved the intestinal barrier function by the upregulation of cell adhesion and relieved intestinal inflammation, thereby exerting a curing effect on colitis in vitro, in vivo, and in an investigator-initiated clinical study of UC. However, how poly P improves mucosal defects induced by intestinal inflammation has not been elucidated. In this study, we detected the accumulation of platelets in inflamed tissues induced by poly P in a dextran sulfate sodium- (DSS-) induced colitis mouse model. A light transmission aggregometry analysis and scanning electron microscopy showed that poly P promoted the platelet aggregation. An SRB assay and ki-67 staining showed that the supernatant of poly P-treated platelet-rich plasma (PRP) increased intestinal epithelial cell growth. A wound healing assay showed that the supernatant of poly P-treated PRP, but not poly P itself, accelerated wound healing. A Western blotting analysis indicated that mitogen-activated protein kinase activation was induced by the supernatant of poly P-treated human PRP in the epithelial cells and its wound healing effect was significantly decreased by the inhibition of ERK signaling. These data suggested that platelet-derived mediators induced by poly P improved intestinal inflammation through the promotion of epithelial cell growth by the activation of the ERK signaling pathway. The mechanism is a novel host-microbe interaction through mammalian platelet-derived mediators induced by bacterial molecules.

scholarly journals A Role for the Mitogen-activated Protein Kinase Kinase Kinase 1 in Epithelial Wound Healing

2006 ◽  
Vol 17 (8) ◽  
pp. 3446-3455 ◽  
Author(s):  
Maoxian Deng ◽  
Wei-Li Chen ◽  
Atsushi Takatori ◽  
Zhimin Peng ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Skin Wound ◽  
Mitogen Activated Protein Kinase ◽  
Epithelial Cell Migration ◽  
Epithelial Wound Healing ◽  
Mitogen Activated Protein ◽  
Pai 1 ◽  
Protein Kinase Kinase

The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell–cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.

scholarly journals Resolvin E1 is a pro-repair molecule that promotes intestinal epithelial wound healing

2020 ◽  
Vol 117 (17) ◽  
pp. 9477-9482 ◽  
Author(s):  
Miguel Quiros ◽  
Darius Feier ◽  
Dorothee Birkl ◽  
Rachit Agarwal ◽  
Dennis W. Zhou ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Wound Repair ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Small Gtpase ◽  
Intestinal Epithelial ◽  
Epithelial Cell Migration ◽  
Cell Migration And Proliferation

Resolution of intestinal inflammation and wound repair are active processes that mediate epithelial healing at mucosal surfaces. Lipid molecules referred to as specialized proresolving mediators (SPMs) play an important role in the restorative response. Resolvin E1 (RvE1), a SPM derived from omega-3 fatty acids, has been reported to dampen intestinal inflammation by promoting anti-inflammatory responses including increased neutrophil spherocytosis and macrophage production of IL-10. Despite these observations, a role for RvE1 in regulating intestinal epithelial cell migration and proliferation during mucosal wound repair has not been explored. Using an endoscopic biopsy-based wound healing model, we report that RvE1 is locally produced in response to intestinal mucosal injury. Exposure of intestinal epithelial cells to RvE1 promoted wound repair by increasing cellular proliferation and migration through activation of signaling pathways including CREB, mTOR, and Src-FAK. Additionally, RvE1-triggered activation of the small GTPase Rac1 led to increased intracellular reactive oxygen species (ROS) production, cell–matrix adhesion, and cellular protrusions at the leading edge of migrating cells. Furthermore, in situ administration of RvE1-encapsulated synthetic targeted polymeric nanoparticles into intestinal wounds promoted mucosal repair. Together, these findings demonstrate that RvE1 functions as a prorepair lipid mediator by increasing intestinal epithelial cell migration and proliferation, and highlight potential therapeutic applications for this SPM to promote mucosal healing in the intestine.

scholarly journals STAT1 coordinates intestinal epithelial cell death during gastrointestinal infection upstream of Caspase-8

2021 ◽  
Author(s):  
Iris Stolzer ◽  
Laura Schickedanz ◽  
Mircea T. Chiriac ◽  
Rocío López-Posadas ◽  
Guntram A. Grassl ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Intestinal Barrier Function ◽  
Caspase 8 ◽  
Intestinal Epithelial ◽  
Gastrointestinal Infection ◽  
Essential Components ◽  
Epithelial Cell Death

AbstractIntestinal homeostasis and the maintenance of the intestinal epithelial barrier are essential components of host defense during gastrointestinal Salmonella Typhimurium infection. Both require a strict regulation of cell death. However, the molecular pathways regulating epithelial cell death have not been completely understood. Here, we elucidated the contribution of central mechanisms of regulated cell death and upstream regulatory components during gastrointestinal infection. Mice lacking Caspase-8 in the intestinal epithelium are highly sensitive towards bacterial induced enteritis and intestinal inflammation, resulting in an enhanced lethality of these mice. This phenotype was associated with an increased STAT1 activation during Salmonella infection. Cell death, barrier breakdown and systemic infection were abrogated by an additional deletion of STAT1 in Casp8ΔIEC mice. In the absence of epithelial STAT1, loss of epithelial cells was abolished which was accompanied by a reduced Caspase-8 activation. Mechanistically, we demonstrate that epithelial STAT1 acts upstream of Caspase-8-dependent as well as -independent cell death and thus might play a major role at the crossroad of several central cell death pathways in the intestinal epithelium. In summary, we uncovered that transcriptional control of STAT1 is an essential host response mechanism that is required for the maintenance of intestinal barrier function and host survival.

Effect of soft foods on primary human gingival epithelial cell growth and the wound healing process

2017 ◽  
Vol 100 ◽  
pp. 433-441 ◽  
Author(s):  
Mahmoud Rouabhia ◽  
Dounia Rouabhia ◽  
Hyun Jin Park ◽  
Luc Giasson ◽  
Ze Zhang
Keyword(s):  
Wound Healing ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Healing Process ◽  
Wound Healing Process ◽  
Gingival Epithelial Cell

scholarly journals Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

2015 ◽  
Vol 309 (12) ◽  
pp. G988-G997 ◽  
Author(s):  
Prashant Nighot ◽  
Rana Al-Sadi ◽  
Manmeet Rawat ◽  
Shuhong Guo ◽  
D. Martin Watterson ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Protein Expression ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Dss Colitis

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/−mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/−mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/−mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/−mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/−mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

Electron Microscopic Study of the Epithelium of the Seminal Vesicle of Aging Rats

1974 ◽  
Vol 32 ◽  
pp. 138-139
Author(s):  
V. F. Allison ◽  
G. C. Fink ◽  
G. W. Cearley
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Seminal Vesicle ◽  
Seminal Vesicles ◽  
Epithelial Layer ◽  
Epithelial Hyperplasia ◽  
Electron Microscopic ◽  
Aging Rats ◽  
Pseudostratified Epithelium

It is well known that epithelial hyperplasia (benign hypertrophy) is common in the aging prostate of dogs and man. In contrast, little evidence is available for abnormal epithelial cell growth in seminal vesicles of aging animals. Recently, enlarged seminal vesicles were reported in senescent mice, however, that enlargement resulted from increased storage of secretion in the lumen and occurred concomitant to epithelial hypoplasia in that species.The present study is concerned with electron microscopic observations of changes occurring in the pseudostratified epithelium of the seminal vescles of aging rats. Special attention is given to certain non-epithelial cells which have entered the epithelial layer.

Platelet Hypersensitivity in Acute Malaria (Plasmodium falciparum) Infection in Man

1981 ◽  
Vol 46 (02) ◽  
pp. 547-549 ◽  
Author(s):  
E M Essien ◽  
M I Ebhota
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Light Transmission ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Wave Pattern ◽  
Falciparum Infection ◽  
Secondary Wave ◽  
Control Subjects ◽  
The Mean

SummaryDuring acute malaria infection, platelets in human platelet-rich plasma are hypersensitive to the addition of ADP between 1.0 uM and 5.0 uM, or adrenaline 0.11 uM as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 uM), 39.8 ± 27 (1SD), was significantly greater than the value in 6 controls (5.2±6.7 (1SD); t = 3, 51 P <0.005). A similar pattern of response was obtained with higher ADP concentrations (2.4,4.5 or 5.0 uM) in 22 patients and 20 control subjects (89.9±14.9% vs 77.8±16.5% (1SD) t = 2.45, P <0.02). Addition of 4.5 uM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls.Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 ± 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2±15.7 ng/ml; t = 13.44, P <0.002).

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