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Published on: November 9, 2018
C9orf72 Alleviates DSS‑Induced Ulcerative Colitis via the cGAS-STING Pathway
Yue Wang1, Ting Xu1, Wenjun Wang2
1Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Purpose:
C9orf72 deficiency contributes to severe inflammation in mice. Ulcerative colitis (UC) is a chronic inflammatory disorder with the shortage of clinical success. However, whether C9orf72 is involved in the progression of UC is not fully understood. This study investigated whether C9orf72 could alleviate dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced colitis in Caco-2 cells.
Methods:
Mice were injected AAV9-C9orf72 lentivirus through tail vein and fed 3% DSS for a week. Caco-2 cells were cultured to establish C9orf723 overexpressed model. Histopathological examination, level of inflammation, cGAS-STING pathway, and gut barrier function were detected in mice and cells.
Results:
C9orf72 overexpression in mice attenuated DSS-induced colitis and intestinal epithelial barrier damage by stimulating ZO-1 and Occludin expression. In LPS-induced Caco-2 cells, C9orf72 overexpression increased cell viability and the expression of ZO-1 and Occludin. C9orf72 overexpression alleviated inflammation by inhibiting the cGAS-STING pathway in colonic tissue and Caco-2 cells.
Conclusion:
C9orf72 overexpression attenuated DSS-induced colitis and intestinal epithelial barrier damage by inhibiting the cGAS-STING pathway. C9orf72 may present a target for mitigating UC.
Insights
C9orf72 overexpression reduced inflammation and gut barrier damage in ulcerative colitis models. This suggests C9orf72 may be a therapeutic target for inflammatory bowel disease.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
- C9orf72 deficiency is linked to severe inflammation, but its role in UC is unclear.
Purpose of the Study:
- To investigate if C9orf72 can alleviate dextran sulfate sodium (DSS)-induced colitis in mice.
- To examine C9orf72's effect on lipopolysaccharide (LPS)-induced colitis in Caco-2 cells.
Main Methods:
- Mice received AAV9-C9orf72 lentivirus and DSS; Caco-2 cells were engineered for C9orf72 overexpression.
- Evaluated histopathology, inflammation markers, cGAS-STING pathway activity, and gut barrier function.
Main Results:
- C9orf72 overexpression attenuated DSS-induced colitis and intestinal barrier damage by upregulating ZO-1 and Occludin.
- In LPS-treated Caco-2 cells, C9orf72 increased cell viability and ZO-1/Occludin expression.
- C9orf72 reduced inflammation by inhibiting the cGAS-STING pathway in both mice and cells.
Conclusions:
- C9orf72 overexpression mitigates DSS-induced colitis and barrier damage via cGAS-STING pathway inhibition.
- C9orf72 shows potential as a therapeutic target for ulcerative colitis.
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