Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model
- 29 May 2016
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 594 (15), 4309-4323
- https://doi.org/10.1113/jp271783
Abstract
Intestinal epithelial barrier (IEB) dysfunctions, such as increased permeability or altered healing, are central to intestinal disorders. Sacral nerve stimulation (SNS) is known to reduce IEB permeability, but its ability to modulate IEB repair remains unknown. This study aimed to characterize the impact of SNS on mucosal repair following TNBS-induced lesions. Six pigs were stimulated by SNS 3 h prior to and 3 h after TNBS enema, while sham animals (n = 8) were not stimulated. The impact of SNS on mucosal changes was evaluated by combining in vivo imaging, histological, and functional methods. Biochemical and transcriptomic approaches were used to analyse the IEB and mucosal inflammatory response. We observed that SNS enhanced the recovery from TNBS-induced increase in transcellular permeability. At 24 h, TNBS-induced alterations of mucosal morphology were significantly less in SNS compared with sham animals. SNS reduced TNBS-induced changes in ZO-1 expression and its epithelial pericellular distribution, and also increased pFAK/FAK expression compared with sham. Interestingly, SNS increased the mucosal density of neutrophils, which was correlated with an increase in trypsin and TGF-β1 levels compared with sham. Finally, SNS prevented the TNBS-induced increases in IL-1β and IL-4 over time that were observed with sham treatment. In conclusion, our results show that SNS enhances mucosal repair following injury. This study highlights novel mechanisms of action of SNS and identifies SNS as a new therapy for diseases with IEB repair disorders. This article is protected by copyright. All rights reservedFunding Information
- Region des Pays de la Loire
This publication has 54 references indexed in Scilit:
- Trypsin Potentiates Human Fibrocyte DifferentiationPLOS ONE, 2013
- Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBDPLOS ONE, 2013
- Central Role of the Gut Epithelial Barrier in the Pathogenesis of Chronic Intestinal Inflammation: Lessons Learned from Animal Models and Human GeneticsFrontiers in Immunology, 2013
- FAK Regulates Intestinal Epithelial Cell Survival and Proliferation during Mucosal Wound HealingPLOS ONE, 2011
- Enteric glia promote intestinal mucosal healing via activation of focal adhesion kinase and release of proEGFAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2011
- Enterocyte Shedding and Epithelial Lining Repair Following Ischemia of the Human Small Intestine Attenuate InflammationPLOS ONE, 2009
- Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouseGut, 2008
- The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent MechanismsThe American Journal of Pathology, 2008
- Trefoil factors: initiators of mucosal healingNature Reviews Molecular Cell Biology, 2003