Zhao Huiqiao, Lu Nianhua, Zhang Yongpeng, Jin Guoyin and He Wei
Background and Objective: Colonic fibrosis is a common and serious complication of Inflammatory Bowel Disease (IBD). The TL1A/DR3 has been shown to be aberrantly expressed in patients with intestinal fibrosis in IBD and may be one of the key regulatory signaling pathways in intestinal fibrosis. The transcription factor ZNF281 has been proposed as a novel player in intestinal inflammation and fibrosis. Previous studies have shown that Gentianopsis paludosa (GP) can alleviate the symptoms of colonic fibrosis in rats, but the mechanism is not completely known. This study focused on the treatment of colonic fibrosis by GP via TL1A/DR3 and ZNF281. Materials and Methods: Lincomycin hydrochloride and 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS) was used to induce colonic fibrosis rat models. As 0.68, 0.34 and 0.17 mg kg1 of GP and salazosulfapyridine (SASP) were used to treat colonic fibrosis rats. The HE staining and Masson staining experiments were performed to evaluate histopathological damage and fibrosis. The expression of fibrosis markers (TGF-β1, α-SMA and ZNF281) were detected by immunohistochemistry and the expression of inflammatory factors (IL-1 and IL-13) were detected by ELISA. Western blotting was applied to detect the expression of TL1A/DR3 signal pathway-related proteins. Results: Lincomycin hydrochloride and TNBS caused significant colonic fibrosis in rats. The SASP and GP significantly reduced colonic tissue damage and fibrosis symptoms. This therapeutic effect was positively correlated with inhibition of TL1A/DR3 and ZNF281 related proteins. Conclusion: The GP ameliorates fibrotic lesions in rats with IBD and is associated with inhibition of the TL1A/DR3 signaling pathway and ZNF281. The GP is expected to be a clinical therapeutic agent for intestinal fibrosis in IBD.
Zhao Huiqiao, Lu Nianhua, Zhang Yongpeng, Jin Guoyin and He Wei, 2024. Gentianopsis paludosa Regulates TL1A/DR3 and ZNF281 to Affect Inflammatory Bowel Disease-Associated Intestinal Fibrosis. International Journal of Pharmacology, 20: 642-651.