The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

2016 ◽  
Vol 310 (11) ◽  
pp. G1118-G1123 ◽  
Author(s):  
Michael Meir ◽  
Sven Flemming ◽  
Natalie Burkard ◽  
Johanna Wagner ◽  
Christoph-Thomas Germer ◽  
...  

Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.


2019 ◽  
Vol 10 (2) ◽  
pp. 1235-1242 ◽  
Author(s):  
Caimei He ◽  
Jun Deng ◽  
Xin Hu ◽  
Sichun Zhou ◽  
Jingtao Wu ◽  
...  

Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases.


2015 ◽  
Vol 308 (12) ◽  
pp. G981-G993 ◽  
Author(s):  
Juan Antonio Rodríguez-Feo ◽  
Marta Puerto ◽  
Carolina Fernández-Mena ◽  
Cristina Verdejo ◽  
José Manuel Lara ◽  
...  

Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10−/− compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10−/− mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.


2010 ◽  
Vol 4 (5) ◽  
pp. 637-651 ◽  
Author(s):  
Susanne A Snoek ◽  
Marleen I Verstege ◽  
Guy E Boeckxstaens ◽  
René M van den Wijngaard ◽  
Wouter J de Jonge

2019 ◽  
Vol 10 (5) ◽  
pp. 2906-2913 ◽  
Author(s):  
Yanlong Li ◽  
Xudong Tian ◽  
Shengcai Li ◽  
Lijun Chang ◽  
Ping Sun ◽  
...  

Dysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome.


2020 ◽  
Vol 11 (9) ◽  
pp. 8077-8088
Author(s):  
Zhenxia Xu ◽  
Wenchao Chen ◽  
Qianchun Deng ◽  
Qingde Huang ◽  
Xu Wang ◽  
...  

Intestinal epithelial barrier dysfunction with dysbiosis of gut microbiota contributes to the occurrence and acceleration of colitis.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Tomasz J. Ślebioda ◽  
Zbigniew Kmieć

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gastrointestinal tract of unclear aetiology of which two major forms are Crohn’s disease (CD) and ulcerative colitis (UC). CD and UC are immunologically distinct, although they both result from hyperactivation of proinflammatory pathways in intestines and disruption of intestinal epithelial barrier. Members of the tumour necrosis factor superfamily (TNFSF) are molecules of broad spectrum of activity, including direct disruption of intestinal epithelial barrier integrity and costimulation of proinflammatory functions of lymphocytes. Tumour necrosis factor (TNF) has a well-established pathological role in IBD which also serves as a target in IBD treatment. In this review we discuss the role of TNF and other TNFSF members, notably, TL1A, FasL, LIGHT, TRAIL, and TWEAK, in the pathogenesis of IBD.


2017 ◽  
Vol 8 (3) ◽  
pp. 1166-1173 ◽  
Author(s):  
Tingting Chen ◽  
Choon Young Kim ◽  
Amandeep Kaur ◽  
Lisa Lamothe ◽  
Maliha Shaikh ◽  
...  

Impaired gut barrier function plays an important role in the development of many diseases such as obesity, inflammatory bowel disease, and in HIV infection.


2021 ◽  
Vol 8 ◽  
Author(s):  
Giovanni Barbara ◽  
Maria Raffaella Barbaro ◽  
Daniele Fuschi ◽  
Marta Palombo ◽  
Francesca Falangone ◽  
...  

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.


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