Xu-Feng Pei1, Long-Lei Cao2, Fang Huang3, Xu Qiao4, Jie Yu2, Hui Ye2, Chang-Lei Xi2, Qi-Chang Zhou2, Guo-Fei Zhang5, Zhi-Lin Gong6. 1. Department of Emergency Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. 2. Department of Anal-colorectal Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. 3. Department of Gynaecology and Obstetrics, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. 4. Department of Gastroenterology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. 5. Department of Gastrointestinal Surgery, Gong'an County People's Hospital in Hubei Province, 434020, China. 6. Department of Anal-colorectal Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China. Electronic address: gong_zhilin@sina.com.
Abstract
OBJECTIVE: miR-22 is known to be involved in the pathogenesis of several autoimmune diseases, but it remains unclear whether miR-22 is associated with inflammatory intestinal disease (IBD). METHODS: The patients with ulcerative colitis (UC) and Crohn's disease (CD) were enrolled in this study. After the CD4+ T cells from healthy controls and active IBD patients were isolated and then transfected with miR-22 mimics/inhibitors, Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure expressions of miR-22, HDAC4, specific transcription factors in intestinal mucosa tissue and CD4+ T cells, while enzyme-linked immuno sorbent assay (ELISA) to detect expressions of inflammatory cytokines in PB. Antisense miR-22 was administered into mice during trinitrobenzene sulphoni cacid (TNBS)-induced colitis to determine its role in IBD. RESULTS: A significant elevation of miR-22 but an evident decrease of HDAC4 was found in CD4+ T cells in PB and intestinal mucosa tissues from IBD patients. In addition, there was a great reduction in HDAC4 and a dramatic enhancement in Th17 cell specific transcription factor (RORC) and inflammatory cytokines (IL-17A, IL-6 and TNF-α) after overexpression miR-22, which was opposite to the effect of inhibition of miR-22. Furthermore, administration of antisense miR-22 in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A+ CD4+ T cells and the expressions of IL-17A, RORC, IL-6 and TNF-α. CONCLUSION: MiR-22 was up-regulated in CD4+ T cells in PB and intestinal mucosa tissues of IBD patients, which could promote Th17 cell differentiation via targeting HDAC4 to be involved in IBD progression.
OBJECTIVE:miR-22 is known to be involved in the pathogenesis of several autoimmune diseases, but it remains unclear whether miR-22 is associated with inflammatory intestinal disease (IBD). METHODS: The patients with ulcerative colitis (UC) and Crohn's disease (CD) were enrolled in this study. After the CD4+ T cells from healthy controls and active IBDpatients were isolated and then transfected with miR-22 mimics/inhibitors, Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure expressions of miR-22, HDAC4, specific transcription factors in intestinal mucosa tissue and CD4+ T cells, while enzyme-linked immuno sorbent assay (ELISA) to detect expressions of inflammatory cytokines in PB. Antisense miR-22 was administered into mice during trinitrobenzene sulphoni cacid (TNBS)-induced colitis to determine its role in IBD. RESULTS: A significant elevation of miR-22 but an evident decrease of HDAC4 was found in CD4+ T cells in PB and intestinal mucosa tissues from IBDpatients. In addition, there was a great reduction in HDAC4 and a dramatic enhancement in Th17 cell specific transcription factor (RORC) and inflammatory cytokines (IL-17A, IL-6 and TNF-α) after overexpression miR-22, which was opposite to the effect of inhibition of miR-22. Furthermore, administration of antisense miR-22 in TNBS-induced mousecolitis model significantly decreased numbers of interleukin (IL)-17A+ CD4+ T cells and the expressions of IL-17A, RORC, IL-6 and TNF-α. CONCLUSION:MiR-22 was up-regulated in CD4+ T cells in PB and intestinal mucosa tissues of IBDpatients, which could promote Th17 cell differentiation via targeting HDAC4 to be involved in IBD progression.
Authors: Zhi Chen; Zhiwei Zhang; Li Guo; Xiaochun Wei; Yang Zhang; Xiaojian Wang; Lei Wei Journal: Bone Joint Res Date: 2020-05-16 Impact factor: 5.853