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Published on: January 5, 2017
Inhibiting Rac1 signaling alleviates DSS-induced colitis by improving inflammatory response and intestinal
Mei-Hong Lin1,2, Can-Hua Luo1,3, Miao-Miao Ma1
1Department of Gastroenterology, The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
Background:
This study aimed to explore the regulation of Ras-related C3 botulinum toxin substrate1 (Rac1) on the intestinal barrier function in colitis and explore its molecular mechanism of regulation on tight junctions.
Methods:
A dextran sulfate sodium (DSS)-induced colitis mouse model was used. The diseases activity index (DAI) was calculated daily. Epithelial permeability was measured. Colon sections were stained with hematoxylin and eosin, and the histological severity was analysed. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyse the messenger ribonucleic acid (mRNA) level of Rac1, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), and occludin in the colon. Western blot was used to detect occludin protein expression.
Results:
Colitis mice showed increased DAI and histological scores, reduced colon length, and impaired epithelial permeability, which were significantly alleviated by the administration of Rac1 inhibitor NSC23766. The level of inflammatory genes including interleukin 6 (IL-6), myeloperoxidase and NOX1 in the colon tissue were elevated in colitis mice, while the administration of NSC23766 remarkably reduced the expression of these genes. Western blot analysis showed that the occludin protein level was suppressed by DSS, while NSC23766 treatment restored the expression of occludin in DSS mice.
Conclusions:
Rac1 inhibitor NSC23766 attenuates symptoms, colonic inflammation, and intestinal permeability in a DSS-induced colitis model. These effects may be attributed to the suppression of inflammatory responses and DSS-induced damage of intestinal integrity.
Insights
Ras-related C3 botulinum toxin substrate1 (Rac1) inhibition alleviates colitis symptoms and improves intestinal barrier function. Rac1 inhibition suppresses inflammatory responses and restores tight junction integrity in a mouse model of colitis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Colitis is characterized by intestinal barrier dysfunction.
- Ras-related C3 botulinum toxin substrate1 (Rac1) plays a role in regulating intestinal barrier function.
- The precise molecular mechanisms of Rac1 in colitis-induced barrier disruption require further elucidation.
Purpose of the Study:
- To investigate the role of Rac1 in regulating intestinal barrier function during colitis.
- To explore the molecular mechanisms by which Rac1 influences tight junctions in colitis.
- To evaluate the therapeutic potential of Rac1 inhibition in a colitis model.
Main Methods:
- A dextran sulfate sodium (DSS)-induced colitis mouse model was established.
- Disease activity index (DAI), epithelial permeability, and histological severity were assessed.
- Gene and protein expression of Rac1, NOX1, and occludin were analyzed using RT-PCR and Western blot.
Main Results:
- DSS-induced colitis mice exhibited increased DAI, histological scores, and impaired epithelial permeability.
- Administration of Rac1 inhibitor NSC23766 significantly alleviated colitis symptoms and improved barrier function.
- NSC23766 treatment reduced inflammatory markers (IL-6, NOX1) and restored occludin protein levels.
Conclusions:
- Rac1 inhibition using NSC23766 attenuates colitis severity and enhances intestinal barrier integrity.
- The protective effects are likely mediated by suppressing inflammatory responses and preserving tight junction proteins.
- Targeting Rac1 represents a potential therapeutic strategy for managing colitis.
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