scholarly journals Effect of Long Noncoding RNA H19 Overexpression on Intestinal Barrier Function and Its Potential Role in the Pathogenesis of Ulcerative Colitis

2016 ◽  
Vol 22 (11) ◽  
pp. 2582-2592 ◽  
Author(s):  
Shan-wen Chen ◽  
Peng-yuan Wang ◽  
Yu-cun Liu ◽  
Lie Sun ◽  
Jing Zhu ◽  
...  
2019 ◽  
Vol 156 (6) ◽  
pp. S-710
Author(s):  
Artin Soroosh ◽  
Carl R. Rankin ◽  
Zulfiqar A. Lokhandwala ◽  
Christos Polytarchou ◽  
Charalabos Pothoulakis ◽  
...  

Author(s):  
Sunil Thomas ◽  
Giancarlo Mercogliano ◽  
George Prendergast

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tangyou Mao ◽  
Junxiang Li ◽  
Lijuan Liu ◽  
Weihan Zhao ◽  
Yuyue Liu ◽  
...  

Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease for which an effective treatment is lacking. Our previous study found that Qingchang Wenzhong Decoction (QCWZD) can significantly improve the clinical symptoms of UC and ameliorate dextran sulphate sodium- (DSS-) induced ulcerative colitis in rats by downregulating the IP10/CXCR3 axis–mediated inflammatory response. The purpose of the present study was to further explore the mechanism of QCWZD for UC in rats models, which were established by 7-day administration of 4.5% dextran sulphate sodium solution. QCWZD was administered daily for 7 days; then we determined the serum macrophage-stimulating protein concentration (MSP) and recepteur d’origine nantais (RON) expression and its downstream proteins (protein kinase B [Akt], phosphorylated [p] Akt, occludin, zona occluden- [ZO-] 1, and claudin-2) in colon tissue using Western blotting and quantitative polymerase chain reaction. In DSS-induced UC, QCWZD significantly alleviated colitis-associated inflammation, upregulated serum MSP expression and RON expression in the colon, reduced the pAkt levels, promoted colonic occluding and ZO-1 expression, and depressed claudin-2 expression. In conclusion, the MSP/RON signalling pathway plays an important role in the pathogenesis of UC by involving the inflammatory response and improving intestinal barrier function. QCWZD appears to attenuate DSS-induced UC in rats by upregulating the MSP/RON signalling pathway.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-Chen E. Hu ◽  
Franziska Weiß ◽  
Christian Bojarski ◽  
Federica Branchi ◽  
Jörg-Dieter Schulzke ◽  
...  

Abstract Background Ulcerative colitis (UC) has a relapsing and remitting pattern, wherein the underlying mechanisms of the relapse might involve an enhanced uptake of luminal antigens which stimulate the immune response. The tricellular tight junction protein, tricellulin, takes charge of preventing paracellular passage of macromolecules. It is characterized by downregulated expression in active UC and its correct localization is regulated by angulins. We thus analyzed the tricellulin and angulin expression as well as intestinal barrier function and aimed to determine the role of tricellulin in the mechanisms of relapse. Methods Colon biopsies were collected from controls and UC patients who underwent colonoscopy at the central endoscopy department of Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin. Remission of UC was defined basing on the clinical appearance and a normal Mayo endoscopic subscore. Intestinal barrier function was evaluated by electrophysiological and paracellular flux measurements on biopsies mounted in Ussing chambers. Results The downregulated tricellulin expression in active UC was recovered in remission UC to control values. Likewise, angulins were in remission UC at the same levels as in controls. Also, the epithelial resistance which was decreased in active UC was restored in remission to the same range as in controls, along with the unaltered paracellular permeabilities for fluorescein and FITC-dextran 4 kDa. Conclusions In remission of UC, tricellulin expression level as well as intestinal barrier functions were restored to normal, after they were impaired in active UC. This points toward a re-sealing of the impaired tricellular paracellular pathway and abated uptake of antigens to normal rates in remission of UC.


2021 ◽  
Author(s):  
Cui Cao ◽  
Bei-Wei Zhu ◽  
Zhengqi Liu ◽  
Xue Wang ◽  
Chunqing Ai ◽  
...  

Ulcerative colitis (UC) is an incurable chronic inflammation of the enteric tract. The aim of this study was to investigate the protective effects of arabinogalactan from Lycium barbarum on DSS-induced...


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