Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. (15th February 2015)

• Record Type: Journal Article
• Authors: Li, Dongmin; Wang, Xuan; Lan, Xi; Li, Yue; Liu, Li; Yi, Jing; Li, Jing; Sun, Qingzhu; Wang, Yili; Li, Hongmin; Zhong, Nannan; Holmdahl, Rikard; Lu, Shemin
• Is Part Of: Molecular and cellular endocrinology. Volume 402(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-02-15
• Subjects: BMC bone marrow cells -- BMM bone marrow-derived macrophages -- DMEM Dulbecco's modification of Eagle's medium -- FBS fetal bovine serum -- HFD high fat diet -- HFD-MetS high-fat-diet induced metabolic syndrome -- miRNA microRNA -- miR-144 microRNA 144 -- NAFLD non-alcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- RT-qPCR real-time quantitative PCR -- TBST Tris-buffer saline with 0.1% Tween -- TLR2 Toll like receptor 2 -- ELISA enzyme-linked immunosorbent assay; miR-144 -- TLR2 -- Proinflammatory cytokines -- Nonalcoholic steatohepatitis (NASH) -- Kupffer cells -- High-fat-diet induced metabolic syndrome (HFD-MetS); Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2014.12.007
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Low miR-144 was negatively correlated with elevated TLR2 which mainly expressed in hepatic Kupffer cells of NASH E3 rats. miR-144 directly targeted 3′UTR of rat TLR2 mRNA. miR-144 negatively regulated TLR2, TNF-α, IFN-γ and activation of NF-κB in NR8383 and BMM cells. Low miR-144 might enhance TNF-α and IFN-γ by targeting TLR2 in NASH of HFD-MetS E3 rats. Abstract: Objective: To analyze regulatory microRNA(s) leading to increased TLR2 expression in livers of high-fat-diet induced metabolic syndrome (HFD-MetS) in rats with non-alcoholic steatohepatitis (NASH). Methods: TLRs, inflammatory cytokines, candidate miRNAs targeting key TLR and its cellular localization were determined in liver. The miR-144 targeting TLR2 and regulating TLR2 signaling were further determined by dual luciferase reporter assay and miR-144 mimics or inhibitor. Results: Expression of miR-144 was negatively correlated with TLR2 expression in Kupffer cells. The miR-144 bound to 3′UTR of rat TLR2 mRNA. In addition, compared to control group, TLR2, TNF-α, IFN-γ and activation of NF-κB decreased after miR-144 mimic challenge in NR8383 cells and BMM from E3 rats, which could be compensated by Pam3CSK4; while opposite effects on their expressions were observed after miR-144 inhibitor administration, augmented by Pam3CSK4. Conclusion: Decreased miR-144 could enhance TNF-α and IFN-γ production by targeting TLR2 in vitro, and might contribute to TLR2 up-regulation and the progression of NASH in HFD-MetS E3 rats. This might offer a novel and potential target for NASH therapy.