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MiR-222-3p Aggravates the Inflammatory Response by Targeting SOCS1 to Activate STAT3 Signaling in Ulcerative Colitis
Fei Xia1, Wenxia Bo1, Jinli Ding1
1Department of Gastroenterology, The Affiliated Jiangning Hospital of Nanjing Medical University, Jiangsu, China.
Background:
Ulcerative colitis is characterized by relapsing inflammation in the gastrointestinal tract with limited treatment options. The aim of the present study was to assess the anti-inflammatory effect of Suppressor of cytokine signaling (SOCS1) on lipopolysac- charide-stimulated RAW264.7 cells and to investigate its potential mechanisms.
Methods:
The in vitro ulcerative colitis model was established by using lipopolysaccharide-stimulated RAW264.7 cells. Western blot- ting was used to detect the protein expression levels of SOCS1, JAK2, STAT3, and VDR. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression of SOCS1, miR-222-3p, and VDR. An enzyme-linked immunosorbent assay was performed to measure the levels of inflammatory cytokines. A luciferase assay assessed the binding of SOCS1 to miR-222-3p. A total of 15 patients with ulcerative colitis and 18 healthy controls were recruited. The expression levels of SOCS1 and miR-222-3p in the colonic mucosa tissues of patients with ulcerative colitis and healthy controls were determined by reverse transcription-quantitative polymerase chain reaction.
Results:
SOCS1 upregulation inhibited the lipopolysaccharide-induced inflammation in RAW264.7 cells. SOCS1 was confirmed to be tar- geted by miR-222-3p. Silencing SOCS1 significantly abolished the inhibitory effects of miR-222-3p downregulation on inflammation. MiR-222-3p activated STAT3 signaling and reduced VDR expression by targeting SOCS1 in lipopolysaccharide-treated RAW264.7 cells. Additionally, miR-222-3p expression was upregulated in ulcerative colitis patients (P = 5.16E-10), while SOCS1 (P = 2.75E-10) and VDR (P = 52.5E-9) expression was downregulated in ulcerative colitis patients. Endoscopic scores (UCEIS) revealed significant positive cor- relation with miR-222-3p and negative correlation with SOCS1 and VDR.
Conclusion:
MiR-222-3p targets SOCS1 to aggravate the inflammatory response by suppressing VDR and activating STAT3 signaling in ulcerative colitis.
Insights
Suppressor of cytokine signaling 1 (SOCS1) inhibits inflammation in ulcerative colitis models. MicroRNA-222-3p targets SOCS1, promoting inflammation by activating STAT3 and reducing VDR, offering potential therapeutic targets.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Ulcerative colitis (UC) involves chronic gastrointestinal inflammation with limited therapeutic options.
- Investigating novel anti-inflammatory mechanisms is crucial for UC treatment.
Purpose of the Study:
- To evaluate the anti-inflammatory role of Suppressor of cytokine signaling 1 (SOCS1) in a cellular model of UC.
- To elucidate the molecular mechanisms underlying SOCS1's action, including its interaction with microRNA-222-3p (miR-222-3p) and Vitamin D Receptor (VDR) signaling.
Main Methods:
- Established an in vitro UC model using lipopolysaccharide-stimulated RAW264.7 cells.
- Utilized Western blotting, RT-qPCR, ELISA, luciferase assays, and patient tissue analysis to assess protein/mRNA expression and cytokine levels.
- Correlated molecular findings with clinical endoscopic scores (UCEIS) in UC patients.
Main Results:
- SOCS1 upregulation demonstrated anti-inflammatory effects in lipopolysaccharide-treated cells.
- miR-222-3p was confirmed to target and downregulate SOCS1, thereby promoting inflammation.
- miR-222-3p activation of STAT3 signaling and VDR suppression was dependent on SOCS1 targeting. UC patients exhibited elevated miR-222-3p and reduced SOCS1 and VDR expression, correlating with disease severity.
Conclusions:
- MiR-222-3p exacerbates UC-related inflammation by targeting SOCS1, leading to STAT3 activation and VDR suppression.
- Targeting the miR-222-3p/SOCS1/VDR axis presents a potential therapeutic strategy for ulcerative colitis.
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