scholarly journals Centella Asiatica Ameliorates Radiation-induced Epithelial Barrier Dysfunction by Secreting Epidermal Growth Factor in Endothelial Cells.

Author(s):  
Seo Young Kwak ◽  
Sehwan Shim ◽  
Won Il Jang ◽  
Seung Bum Lee ◽  
Min-Jung Kim ◽  
...  

Abstract BackgroundRadiation-induced intestinal damage is frequently observed following radiotherapy for abdominal and pelvic cancer or occurs due to radiation exposure in a nuclear accident. In an effort to overcome radiation-induced normal tissue damage, a variety of radio-mitigator candidates have been investigated. The loss of the epithelium and its barrier function leads to ‘leaky gut’, so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine in Chinese culture, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on crosstalk between endothelial and epithelial cells.ResultsCA treatment attenuated radiation-induced endothelial dysfunction in human umbilical vein endothelial cells and mitigated radiation-induced enteropathy in a mouse model. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered loss of epithelial integrity by regulating zonula occludens 1 and desmoglein 2 in radiation exposure. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF, which can mimic the effect of CA-induced secretion in irradiated endothelial cells, effectively improved the radiation-induced epithelial barrier dysfunction. In addition, blockade of EGF in CA-induced endothelial secretome impeded epithelial barrier recovery. Finally, we identified the therapeutic effects of CA-induced endothelial secretome in a radiation-induced enteropathy mouse model with epithelial barrier restoration.ConclusionsWe have shown therapeutic effects of CA on radiation-induced enteropathy, with the recovery of endothelial and epithelial dysfunction, focusing on the crosstalk between endothelial cells and epithelial cells. Thus, our finding suggest that CA is an effective radio-mitigator against radiation-induced enteropathy.

2008 ◽  
Vol 76 (8) ◽  
pp. 3390-3398 ◽  
Author(s):  
Jennifer M. Lamb-Rosteski ◽  
Lisa D. Kalischuk ◽  
G. Douglas Inglis ◽  
Andre G. Buret

ABSTRACT Campylobacter jejuni is a leading cause of acute bacterial enteritis in humans. Poultry serves as a major reservoir of C. jejuni and is thought to act as a principal vehicle of transmission to humans. Epidermal growth factor (EGF) is a small amino acid peptide that exerts a broad range of activities on the intestinal epithelium. The aims of this study were to determine the effect of EGF on C. jejuni intestinal colonization in newly hatched chicks and to characterize its effects on C. jejuni-induced intestinal epithelial barrier disruption. White Leghorn chicks were treated with EGF daily, starting 1 day prior to C. jejuni infection, and were compared to control and C. jejuni-infected, EGF-treated chicks. Infected chicks shed C. jejuni in their feces throughout the study period. C. jejuni colonized the small intestine and cecum, disseminated to extraintestinal organs, and caused jejunal villus atrophy. EGF reduced jejunal colonization and dissemination of C. jejuni to the liver and spleen. In EGF-treated C. jejuni-infected chicks, villus height was not significantly different from that in untreated C. jejuni-infected chicks or controls. In vitro, C. jejuni attached to and invaded intestinal epithelial cells, disrupted tight junctional claudin-4, and increased transepithelial permeability. C. jejuni also promoted the translocation of noninvasive Escherichia coli C25. These C. jejuni-induced epithelial abnormalities were abolished by pretreatment with EGF, and the effect was dependent upon activation of the EGF receptor. These findings highlight EGF's ability to alter colonization of C. jejuni in the intestinal tract and to protect against pathogen-induced barrier defects.


2003 ◽  
Vol 194 (2) ◽  
pp. 139-150 ◽  
Author(s):  
Francesco Moccia ◽  
Roberto Berra-Romani ◽  
Simona Tritto ◽  
Silvia Signorelli ◽  
Vanni Taglietti ◽  
...  

2010 ◽  
Vol 51 (5) ◽  
pp. 535-541 ◽  
Author(s):  
Haejin OH ◽  
Jinsil SEONG ◽  
Wonwoo KIM ◽  
Sooyeon PARK ◽  
Woong Sub KOOM ◽  
...  

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