<scp>ERK1/2</scp> participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis

Tan, Jia Cheng; Cui, Wen Xia; Heng, Ding; Lin, Lin

doi:10.1111/1751-2980.12163

Cited by 13 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 1999, Omura and colleagues (16) established an animal model of EE, induced surgically in rats. This model has enabled advances in the pathophysiology of EE (22) and provided the information required to search for compounds that can effectively treat this disease. Despite the high prevalence of NERD, there are very few animal models that can mimic the pathophysiological features observed in these patients.…”

Section: Discussionmentioning

confidence: 99%

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity

Silva

Oliveira

Bingana

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD. In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity

Silva

Oliveira

Bingana

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Posttranslational modification of tight junction proteins is responsible for tight junction function . ERK activation regulates the expression and distribution of tight junction proteins . Cong et al demonstrated that clau‐4 is phosphorylated by ERK activation to trigger clau‐4 internalization .…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, knockdown or knockout of PAR‐2 inhibits the phosphorylation of ERKs . Moreover, ERKs (serine/threonine protein kinases) regulate the expression and distribution of tight junction proteins . Cong et al reported that ERK activation phosphorylates clau‐4 to recruit β‐arrestin 2 and then interacts with clathrin to promote clau‐4 internalization .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Yang

Yao

et al. 2019

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Intestinal barrier dysfunction is a key etiologic factor of irritable bowel syndrome (IBS). Metformin improves intestinal barrier function, although the underlying mechanism has yet to be fully explained. This study evaluates the protective effect of metformin on colonic barrier integrity and explores the underlying cellular mechanisms. Methods IBS‐like rats were induced by maternal separation. Metformin was administered daily by gavage at 08:30, and rat pups were then separated from their mother. Visceral hyperalgesia and depression‐like behaviors were evaluated by colorectal distension, sucrose preference tests, and forced swimming tests. Intestinal integrity was analyzed using sugar probes and transmission electron microscopy. Inflammatory factors and the levels of corticotropin‐releasing factor were assessed by PCR and ELISA. The number of mast cells was evaluated by toluidine blue staining. Protein expression and localization were determined using Western blot and immunochemistry. Key Results Metformin pretreatment (a) reduced visceral hypersensitivity to colorectal distension, immobility time and enhanced sucrose consumption; (b) decreased urine lactulose/mannitol ratio and sucralose output; (c) inhibited the dilation of tight junction and prevented claudin‐4 translocation; (d) inhibited mast cell activation and downregulated the expression of IL‐6, IL‐18, tryptase, PAR‐2, and ERK activation; (e) inhibited claudin‐4 phosphorylation at serine sites and interactions between clau‐4 and ZO‐1. Conclusions & Inferences Metformin may block mast cell activation to reduce PAR‐2 expression and subsequently inhibit ERK activation and clau‐4 phosphorylation at serine sites to normalize the interaction of clau‐4 and ZO‐1 and clau‐4 distribution. Metformin may be clinically beneficial for patients with IBS or IBS‐like symptoms.

show abstract

“…15,16 Changes in the amount and distribution of these proteins changes the paracellular permeability and is associated with alterations of the intercellular space between cells. 17 When this space becomes dilated, there is evidence that this can result in increased paracellular entry of intraluminal contents, such as acidic refluxate. 18 Severe dilation may also be associated with abrogation of tight junctions.…”

Section: Interaction Between Bmi and Reflux With Overall Mnbimentioning

confidence: 99%

Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms

Blevins

Dierkhising

Geno

et al. 2018

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

ERK1/2 participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis

Abstract: TJ proteins could be used as sensitive markers of RE instead of DIS. ERK1/2 may participate in regulating TJ proteins in esophageal epithelia in RE.

Cited by 13 publications

References 37 publications

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms

Contact Info

Product

Resources

About