Qian Zhang1, Kun Yu2, Yazhen Cao3, Yanli Luo1, Yan Liu1, Caiyan Zhao4. 1. Department of geriatrics, the third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 2. Medical General Laboratory, the third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 3. Department of Cardiology Ward, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, China. 4. Department of Infectious diseases, the third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Electronic address: zhaocaiyanhub@yeah.net.
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high incidence and mortality rate, and a rapid course of clinical development. Although miR-125b is closely associated with the pathogenesis of liver fibrosis and hepatocellular carcinoma, the role of miR-125b in NAFLD remains unknown. METHODS: The levels of TNF-α, IL-6, and IL-1β expression were examined via ELISA assays. Real-time PCR was used to determine the levels of miR-125b and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression. The related molecular mechanisms were examined by performing luciferase reporter, western blot, and immunofluorescence assays. Structural changes in the livers of mice with NAFLD were observed via H&E staining. RESULTS: The levels of TNF-α, IL-6, and IL-1β in NAFLD patients were greatly increased, and miR-125b expression was significantly up-regulated. The phosphorylation of IκBα and p65, and secretion of inflammatory factors were all markedly decreased by miR-125b silencing, but greatly increased by miR-125b overexpression. We also demonstrated that downregulation of TNFAIP3 in NAFLD was negatively correlated with miR-125b. Interestingly, the influence of miR-125b inhibitors on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammatory responses were greatly aggravated by co-treatment with TNFAIP siRNA; however, the opposite results were obtained after treatment with miR-125b mimics and TNFAIP plasmids. Furthermore, the HF-induced liver damage and inflammatory responses were greatly ameliorated by miR-125b inhibitors but further aggravated by co-treatment with TNFAIP3 siRNA. CONCLUSION: MiR-125b promoted the NF-κB-mediated inflammatory response in NAFLD by directly targeting TNFAIP3, and that mechanism might be target for treating NAFLD.
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) has a high incidence and mortality rate, and a rapid course of clinical development. Although miR-125b is closely associated with the pathogenesis of liver fibrosis and hepatocellular carcinoma, the role of miR-125b in NAFLD remains unknown. METHODS: The levels of TNF-α, IL-6, and IL-1β expression were examined via ELISA assays. Real-time PCR was used to determine the levels of miR-125b and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression. The related molecular mechanisms were examined by performing luciferase reporter, western blot, and immunofluorescence assays. Structural changes in the livers of mice with NAFLD were observed via H&E staining. RESULTS: The levels of TNF-α, IL-6, and IL-1β in NAFLD patients were greatly increased, and miR-125b expression was significantly up-regulated. The phosphorylation of IκBα and p65, and secretion of inflammatory factors were all markedly decreased by miR-125b silencing, but greatly increased by miR-125b overexpression. We also demonstrated that downregulation of TNFAIP3 in NAFLD was negatively correlated with miR-125b. Interestingly, the influence of miR-125b inhibitors on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammatory responses were greatly aggravated by co-treatment with TNFAIP siRNA; however, the opposite results were obtained after treatment with miR-125b mimics and TNFAIP plasmids. Furthermore, the HF-induced liver damage and inflammatory responses were greatly ameliorated by miR-125b inhibitors but further aggravated by co-treatment with TNFAIP3 siRNA. CONCLUSION:MiR-125b promoted the NF-κB-mediated inflammatory response in NAFLD by directly targeting TNFAIP3, and that mechanism might be target for treating NAFLD.
Authors: Gloria M Gager; Ceren Eyileten; Marek Postula; Aleksandra Gasecka; Joanna Jarosz-Popek; Georg Gelbenegger; Bernd Jilma; Irene Lang; Jolanta Siller-Matula Journal: Front Cardiovasc Med Date: 2022-07-08
Authors: Zaida Zakaria; Zaidatul Akmal Othman; Joseph Bagi Suleiman; Nur Asyilla Che Jalil; Wan Syaheedah Wan Ghazali; Victor Udo Nna; Mahaneem Mohamed Journal: Antioxidants (Basel) Date: 2021-12-20