J-P Wang1, L-N Dong, M Wang, J Guo, Y-Q Zhao. 1. Department of Gastroenterology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, China. wangjp8396@126.com.
Abstract
OBJECTIVE: To study the effect of micro ribonucleic acid (miR)-146a on the development of ulcerative colitis (UC) and to explore its regulatory effect on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB) signaling pathways. MATERIALS AND METHODS: The UC model in rats was established using 2,4,6-trinitrobenzenesulfonic acid (TNBS)/ethanol. A total of 30 male rats were randomly divided into control group, model group and miR-146a inhibitor group, with 10 rats in each group. The disease activity index (DAI) and the macroscopic score of colonic mucosa were measured in each rat. MiR-146a expression in rat intestinal tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rats were detected via enzyme-linked immunosorbent assay (ELISA). Additionally, Western blotting assay was performed to detect protein levels of TLR4, MyD88, and NF-κB in rat intestinal tissues. RESULTS: Compared with those in control group, rats in model group had notably increased DAI, inflammation score, upregulated expression levels of TLR4, MyD88, NF-κB, and miR-146a, as well as increased serum levels of IL-1β and TNF-α. However, rats in miR-146a inhibitor group exhibited substantially decreased DAI, inflammation score, lowered content of IL-1β and TNF-α and levels of TLR4, MyD88, and NF-κB compared with those in model group. CONCLUSIONS: We found that miR-146a inhibitor alleviates UC by reducing the release of inflammatory factors through suppressing the TLR4/MyD88/NF-κB signaling pathway.
OBJECTIVE: To study the effect of micro ribonucleic acid (miR)-146a on the development of ulcerative colitis (UC) and to explore its regulatory effect on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB) signaling pathways. MATERIALS AND METHODS: The UC model in rats was established using 2,4,6-trinitrobenzenesulfonic acid (TNBS)/ethanol. A total of 30 male rats were randomly divided into control group, model group and miR-146a inhibitor group, with 10 rats in each group. The disease activity index (DAI) and the macroscopic score of colonic mucosa were measured in each rat. MiR-146a expression in rat intestinal tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rats were detected via enzyme-linked immunosorbent assay (ELISA). Additionally, Western blotting assay was performed to detect protein levels of TLR4, MyD88, and NF-κB in rat intestinal tissues. RESULTS: Compared with those in control group, rats in model group had notably increased DAI, inflammation score, upregulated expression levels of TLR4, MyD88, NF-κB, and miR-146a, as well as increased serum levels of IL-1β and TNF-α. However, rats in miR-146a inhibitor group exhibited substantially decreased DAI, inflammation score, lowered content of IL-1β and TNF-α and levels of TLR4, MyD88, and NF-κB compared with those in model group. CONCLUSIONS: We found that miR-146a inhibitor alleviates UC by reducing the release of inflammatory factors through suppressing the TLR4/MyD88/NF-κB signaling pathway.
Authors: Suruchi K Batra; Christopher R Heier; Lina Diaz-Calderon; Christopher B Tully; Alyson A Fiorillo; John van den Anker; Laurie S Conklin Journal: Inflamm Bowel Dis Date: 2020-09-18 Impact factor: 5.325