Interleukin-22 Ameliorates Dextran Sulfate Sodium-Induced Colitis through the Upregulation of lncRNA-UCL to Accelerate Claudin-1 Expression via Sequestering miR-568 in Mice.

Background: Bioactive compound such as interleukin-22 (IL-22) treatment is regarded as a sufficient treatment for ulcerative colitis (UC). It has been found that long noncoding RNAs (lncRNAs) expressed in many inflammatory diseases, including UC. We aimed to verify the treatment effect of bioactive compounds including IL-22 and lncRNAs in UC on colitis mice.

Methods: UC mice were induced using DSS, followed by IL-22 or PBS intraperitoneally (i.p.) injection. Then, the histopathological parameters of the mice were determined. Then, RNA sequencing was performed to screen the differential lncRNAs. Quantitative real-time PCR (qRT-PCR) and lentivirus identified lncRNA-Ulcerative Colitis lncRNA (lncRNA-UCL) were regarded as the molecular regulator of the colitis mice. The correlation with lncRNA-UCL and mmu-miR-568 was validated using RNA-pulldown. Meanwhile, claudin-1 was predicted and confirmed as the target molecule of mmu-miR-568 using dual-luciferase assay.

Results: IL-22 could significantly improve the histopathological features and decrease proinflammatory cytokine production in UC mice induced by DSS. It also can stimulate intestinal epithelial cell (IEC) reproduction and prevention of apoptosis. lncRNA-UCL was significantly downregulated in UC mice caused by DSS, while IL-22 treatment effectively reversed this effect. In terms of mechanism, lncRNA-UCL regulates intestinal epithelial homeostasis by sequestering mmu-miR-568 and maintaining close integrated protein expression, such as claudin-1.

Conclusions: We have demonstrated the incredible role of bioactive compound, such as IL-22, in alleviating DSS-induced colitis symptoms via enhancing lncRNA-UCL expression. It can be regulated using tight junction (TJ) protein.