Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis |
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Authors: | Lian-Zhen Yu Hai-Yang Wang Shu-Ping Yang Zhi-Ping Yuan Fang-Yuan Xu Chao Sun Rui-Hua Shi |
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Institution: | Lian-Zhen Yu, Shu-Ping Yang, Zhi-Ping Yuan, Fang-Yuan Xu, Chao Sun, Rui-Hua Shi, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaHai-Yang Wang, Department of Internal Medicine, Affiliated Mingde Hospital of Nanjing Medical University, Nanjing 211166, Jiangsu Province, China |
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Abstract: | AIM: To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis.
METHODS: Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p-STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting.
RESULTS: Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.
CONCLUSION: IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC. |
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Keywords: | Ulcerative colitis Ulcerative colitis-related carcinogenesis Interleukin-22 Interleukin-22R1 STAT3 |
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