Related Experiment Video
Updated: Aug 25, 2025
Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
Published on: January 5, 2017
circSMAD4 Promotes Experimental Colitis and Impairs Intestinal Barrier Functions by Targeting Janus Kinase 2 Through
Jie Zhao1, Zhiliang Lin2, Pu Ying3
1Department of Gastrointestinal Surgery and and Central Laboratory, Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.
Background:
Numerous studies have explored the association between circular RNAs [circRNAs] and Crohn's disease [CD]. However, the pathological role, biological functions, and molecular mechanisms of circRNAs in CD have not been fully elucidated.
Methods:
The circRNA microarray analysis was performed to identify deregulated circRNAs in colon tissues. The identified circRNAs were verified through quantitative real-time polymerase chain reaction [qRT-PCR]. In vivo and in vitro functional studies were performed to verify the role of circSMAD4 in CD and investigate the mechanisms involved.
Results:
We found that circSMAD4 was the most significantly upregulated circRNA. The expression level of circSMAD4 was positively correlated with levels of inflammatory factors. Overexpression of circSMAD4 impaired tight junction [TJ] proteins and enhanced apoptosis of epithelial cells. These effects were reversed by treatment with miR-135a-5p mimic. Mechanistic studies showed that circSMAD4 exerts its effects on CD by 'sponging' miR-135a-5p to regulate Janus kinase 2 [JAK2]. Si-circSMAD4 delivery through microspheres ameliorated experimental colitis and protected the intestinal barrier function in IL-10 knockout mice.
Conclusion:
This study shows that circSMAD4 regulates the progression of experimental colitis via the miR-135a-5p/JAK2 signalling axis and it may be a potential therapeutic target.
Insights
Circular RNA SMAD4 (circSMAD4) promotes Crohn's disease progression by regulating the miR-135a-5p/JAK2 pathway. Targeting circSMAD4 may offer a new therapeutic strategy for Crohn's disease.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Crohn's disease (CD) pathogenesis involves complex molecular mechanisms.
- Circular RNAs (circRNAs) are implicated in CD, but their specific roles remain unclear.
Purpose of the Study:
- To investigate the role and mechanism of circSMAD4 in Crohn's disease.
- To identify circRNAs associated with CD and their downstream targets.
Main Methods:
- circRNA microarray analysis of colon tissues.
- Quantitative real-time PCR (qRT-PCR) for verification.
- In vivo and in vitro functional assays, including microsphere delivery in IL-10 knockout mice.
Main Results:
- circSMAD4 was significantly upregulated in CD and correlated with inflammatory factors.
- circSMAD4 overexpression disrupted epithelial barrier integrity and increased apoptosis.
- circSMAD4 acts as a molecular sponge for miR-135a-5p, regulating Janus kinase 2 (JAK2) signaling.
- Silencing circSMAD4 ameliorated experimental colitis and protected intestinal barrier function.
Conclusions:
- circSMAD4 promotes experimental colitis via the miR-135a-5p/JAK2 axis.
- circSMAD4 represents a potential therapeutic target for Crohn's disease.
More Related Videos
Related Concept Videos
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...